 Good morning class, so welcome to another discussion for our immunology serology class, so for today we will be continuing our discussion about the immunological disorder, so last meeting we talked about your hypersensitivity, so hopefully you are already understanding what hypersensitivity is all about, so that is chapter 14 of your Stevens. Now let's move forward to chapter 15 and this can be found on page 266 of your Stevens. So for this morning we will be talking about your first autoimmune disease, okay. We'll be talking about what is autoimmune disorders to start up to first starters and then we will be discussing what is your systemic lupus erythematosus. Again, for the succeeding classes we'll be talking about the other autoimmune diseases and then finish up our lecture for this week. So let's get started and let's go straight ahead to our discussion. So when we talk about autoimmune disorders, this is a particular condition in which damage to organs or tissues are the results of having or because of the presence of autoantibody or auto reactive cells. So always remember that our immune system is very much capable of reacting to foreign substances which we call your antigens or immunogens. So our body specifically your immune system defends us from microorganisms that might cause infection. And last meeting when we talk about hypersensitivity, we talk about how our immune system can respond negatively or exaggeratedly to harmless antigens. Now when we talk about autoimmune disorders, we do have now an autoimmune response to our own self or to our own antibody. And with this, okay with this as Paul earlier described this phenomenon, this is horror ototoxicosis or meaning fear of self poisoning. Why self poisoning or why horror ototoxicos? Because our own immune system is attacking our own tissue or our own organs. Now, for us to be able to understand autoimmune disorder, let us talk about first some important terms that we need to know before we dig into the different autoimmune disorders. Now, in a normal individual without autoimmune disorder, each and every one of us has self tolerance. Now what is self tolerance? Self tolerance is the ability of our immune system to accept self antigen. So all I want you guys to remember that even our body, we do contain different antigens, our cells have different glycoproteins on its surface. And those are also considered antigen, but because we do have self tolerance, our immune system do not initiate an immune response. Okay, our immune system do not initiate a response against them. Why? Because it is our own. If you guys could remember your natural killer cell. Our natural killer cell is capable of identifying our own cells from those virally infected cells. That's why it is able to tolerate those antigens coming from our body. Similarly, in a wider scale, our immune system is also capable of that. And that is what we call self tolerance. And when we talk about self tolerance, again, this is the ability of our immune system to accept self antigens. That's why when you have autoimmune disease, when you have autoimmune disease, it is because of a result of your loss of self tolerance. Your immune system can no longer tolerate our own or our self antigen. That's why they respond negatively to these antigens. And there are two types of tolerance. We have central tolerance and we also have your peripheral tolerance. When we say central tolerance, this occurs in our central lymphoid organs. It occurs in our central lymphoid organs such as your thymos and even your bone marrow. If you guys could remember when we talk about your T cell differentiation, there is a very scrutinized process where our T lymphocytes go through. Sometimes, if these lymphocytes are against or if they react to our self antigen, they are deleted. This is now your clonal selection if you guys would remember in your T cell differentiation. It is a very tedious process in which your T cell are scrutinized and only a little percentage of your T cell are passing that stage. Kokoontik lang yung mga T lymphocytes natin that are capable of accomplishing or passing through that stage when it comes to your T cell differentiation. Now, please do remember that your central tolerance, when it comes to your central tolerance, as your T cell mature, they would encounter self antigens. And if they react with the self antigen, they will be deleted. Again, if they react to our self antigen, they will be deleted. This is the process of central tolerance. Now, we also do have your peripheral tolerance. When we say peripheral tolerance, these now is the process that is happening on your secondary lymphoid organs. So, what are your secondary lymphoid organs? All other organs aside from your bone marrow and your thymus that are belonging to your immune system. Your spleen, your lymph nodes, your pares patches, those are your secondary lymphoid organs. And the same thing, when your lymphocytes are also reactive, if your lymphocytes are also reactive to your self antigen, they will also get deleted. So, the bottom line about self tolerance is that if you have an immune component, specifically our lymphocytes. If your lymphocytes are attacking our self antigen, our own cells, our own tissue, they will be deleted. Now, if you lost this capability, if your self tolerance is no longer in place or is no longer normal, then that's the time that you develop autoimmune disorders. You develop autoimmune disorders. So, that's one scenario in which you can develop autoimmune diseases. You can develop autoimmune diseases. Of course, there are also other factors such as genetics. If you guys could remember your major histocompatibility complex in the short arm of your chromosome 6, there are different loci of your gene. And if you have a specific mutation on those genes, it can lead to the development of an autoimmune disease. Take for example, your type 1 diabetes, the name of you. So, all of those are your alkaloating spondylitis. So, those are diseases because of autoimmune diseases because of genetics. Now, there are also other cases in which your autoimmune diseases are due to other influence of other endogenous and environment. So, some it can be because of your hormonal influences. It can also be because of tissue trauma or release of cryptic antigens. When we say cryptic antigens, these are hidden antigens in our tissue that when it's released, it elicit an immune response. Thereby, attacking our own cells in our own tissue. Now, aside from hormonal influence, tissue trauma that leads to the release of your cryptic antigen, it can also be because of your microbial infections. Now, what about microbial infection? Remember that when it comes to microbial infection, there is what we call your molecular mimicry. Okay, when we say molecular mimicry, there are some individual viral or bacterial agent that contains antigen that closely resemble our own antigen. So, when we say molecular mimicry, it's very much synonymous to your cross-reactivity. Now, there are some bacteria, there are some viruses that contains antigen. Antigen in these microorganisms or in these pathogens that resemble our self-antigen. A good example of that will be your polyovirus VP2 that resembles your acetylcholine. And acetylcholine is a very common molecule within our body specifically in our nervous system. Now, we also have your measles virus P3 that resemble the myelin basic protein of our nerves. And you also have papilloma virus VP2 which resembles your insulin receptors. Now, because of this molecular mimicry, okay, because of this molecular mimicry, take for example, you have polyovirus, measles virus or papilloma virus. These viruses, they elicit or they trigger our immune system to develop or to release an antibody directed against them. And because of molecular mimicry, because of these, the antigen of these viruses resemble our own antigen, what happened now is that there is a possibility that the antibody that is supposed to bind or attack your polyovirus, it can also now attack your acetylcholine. And the same thing is true when it comes to measles. The antibody for your measles virus can now react with your myelin basic protein, your papilloma virus antigen can now react with your insulin receptors. And because of this molecular mimicry, okay, and because of this molecular mimicry, we now have what we call your bystander effect. Okay, these bystander effect happens when your microorganism induce a local inflammatory response that recruits leukocytes and stimulate your antigen-presenting cell to release cytokines that activate your t-cell. Okay, activate your t-cell. This is the way on how your organism can cause autoimmunity. Now, take for example, you have your polyovirus or polyovirus would cause a local inflammatory response. Recruiting your leukocytes, your antigen-presenting cells, thereby releasing your cytokines that activates your t-cell. Now, because the antibody that will be produced can also bind not only to your polyovirus but also to your acetylcholine, it can now cost now your autoimmunity. And this is how your microorganisms, okay, in the bystander effect, okay, your bystander effect, this is how your organisms, specifically your microorganisms, your microorganisms, causes autoimmunity. Okay, they causes autoimmunity. So, with this mechanism, because of the molecular mimicry, because they are structurally similar, okay, with our self-antigen, instead of the microorganism, instead of the microorganisms being attacked by those antibody and by those cytokines, our self-antigens are the one being attacked now, our own cells, our own tissue is the one being attacked now. So, with this, okay, autoantipot, autoimmunity can develop, okay, autoimmunity can develop. So, that's how your microorganism, that's one way or on how your microorganisms, okay, that's one way how your microorganisms causes your autoimmunity. So, aside from molecular mimicry, they can also have bystander effect, and aside from that, they are the third way or the third manner on how microorganisms induce, okay, will probably induce autoimmunity is through your super antigens. So, super antigens, these are proteins, okay, these are proteins that are produced by various microorganisms that has the ability, okay, it has the ability to bind to both your major histocompatibility complex class 2 and your TCRs, okay, your TCR. So, when your TCRs, okay, when your TCRs and your MHC class 2, okay, when your TCR and your MHC class 2, okay, again going back, okay, your super antigens, this is another way on how your microorganism induce an autoimmunity or rather autoimmune disorders. Now, the super antigens are also proteins that are capable of binding to both your MHC or your major histocompatibility complex class 3 and your TCRs. Again, TCRs this are your T cell receptors, okay, regardless of the antigens specificity. So, with the super antigens, okay, with the super antigens, they can cause a nonspecific activation of your T cell resulting to the activation of your polyclonal T cell and because of the multiplication of your T cell, okay, because your T cell now will proliferate upon activation, it can release a massive cytokine. And remember, your cytokines can cause cytokine storm thereby affecting our own tissue and our cells. So again, our microorganisms, our microorganisms can lead to autoimmunity by molecular mimicry, by bystander effect and by causing super antigens. Now, if you want to read more about that, you can go to your chapter 13 that can be found around page 268 on WARS, okay, 268 on WARS. But moving forward, okay, I hope I was able to further explain to you guys the basic on how our self-tolerance and also other factors like hormones, genetics, your cryptic antigens, and also your microorganisms can lead to autoimmunity. Now, when we talk about autoimmunity then, okay, when we talk about your autoimmunity, it can be further classified into two, okay, it can be further classified into two. So what are those two classifications of your autoimmunity? They can be organ specific or they can also be systemic or non-organ specific. When we talk about organ specific, it only affects a specific organ like they, for example, it only affects your pancreas, your thyroid, or a specific organ inside our body. Unlike some of your autoimmune disorders, they can also be systemic meaning to say they are non-organ specific like your systemic lupus erythematosus that can manifest in various organs in your oral, oral cavities in your skin. It can also affect your heart, your lungs, your kidney, even your blood, your muscles, and even your joints. Now, for this particular lecture, we will be starting off and we'll be discussing first your systemic autoimmune diseases, specifically your systemic lupus erythematosus. Now, for the next discussion on our synchronous class, I will be talking about your rheumatoid arthritis on our next lecture. But for now, let's talk about your systemic autoimmune diseases to start off. Let's talk about your lupus erythematosus, okay, your lupus erythematosus. So these are the examples of your systemic autoimmune diseases. We have your systemic lupus erythematosus, your rheumatoid arthritis, and you also have your granulomatosis with polyangitis or your wedging nurse granulomatosis. Now, for our discussion for today, we'll be talking about your systemic lupus erythematosus. So your systemic lupus erythematosus, being a systemic autoimmune disease, it involves multiple system, multiple organ systems in an individua. So immune complex disease, it is an immune complex disease characterized by the overproduction of your autoantibodies. So there are a lot of autoantibodies produced in your systemic lupus erythematosus. That's why also the reason why there are a lot of organ system that are involved when we talk about your SLE. Now, we're going to talk about the different autoantibodies later on as we also talk about how we diagnose or how we identify the presence of an auto of your SLE in a particular individua. Now, your systemic lupus erythematosus has a common manifestation as arthritis. Arthritis is the most common manifestation of your SLE. That's why a lot of people with mistaken it means sand as your rheumatoid arthritis, but those are two entirely different autoimmune disease. So if you get rid of your book and other references, your systemic lupus erythematosus are usually appearing around the age of 40 years old. If you're 40 and above, that's the time where your SLE is most common to appear. Now, your SLE is also manifesting not only as an arthritis, but it can also manifest itself as a skin lesion. So a characteristic, a distinct characteristic of patients with systemic lupus erythematosus is the presence of a butterfly rash. That's why patient that are having your SLE are also termed as your red wolf. So what is this characteristic butterfly rash that are usually seen in patient with SLE? So as you can see on your screen right now, this is your butterfly rash. This is not just a simple nut blush ka or this is not just a simple sand burn. This are really rash on your nose and your cheeks. This butterfly rash or the red rash or the butterfly rash that you usually see in your patients is a distinct characteristic among patient with systemic lupus erythematosus. So always remember that this butterfly rash is very distinct when it comes to your SLE. So again, aside from your butterfly rash, I also want you guys to remember that patients with SLE are usually women. Women are most likely to be affected than men. So nine is to ten is the ratio. So nine women and one nine is the ratio of SLE women to men. Women to men is nine is to one. So some na kababa ihan. Nine out of ten are women and only one out of ten are men. Are men having your SLE. Now it's very important that for you guys to remember the characteristic rash for your SLE again is your butterfly rash. Now having said that that your systemic lupus erythematosus is because of the presence of your autoantibodies that can be because of the loss of your self-tolerance, probably because of hormonal factors, because of your sometimes because it can also be idiopathic. Idiopathic meaning to say there is no known reason on to why you're having your autoimmune or you're having your SLE. But in women, if you guys could remember, we talk about your hormones. Now in women, estrogen is one of the playing factor in the development of your systemic lupus erythematosus. But not only hormones, sometimes it can also be unknown cause or idiopathic. But there are also drugs that are associated mainly to your lupus. So drugs like prochinamide, your hydrelazine, your chlorpromazine, your isoniazid and your kinadine. These are drugs that can cause your systemic lupus erythematosus. Now it's important to balance the clinical manifestation but also the immunologic criteria for your SLE. So here is the criteria for your SLE. So we have your clinical and of course your immunologic criteria. When we say clinical, these are the signs and symptoms that are usually seen in your patient. And when we talk about your immunological criteria, we are not talking about the different laboratory tests or different laboratory results that we can observe among patients with SLE. Now to further explain this, we will now be talking about the laboratory diagnosis. Of course when it comes to the clinical manifestation, there are different signs and symptoms as you can see. It ranges from your oral cavity, your skin, literary systemic impact in our patient. Now since we are medical technologists, let's focus in, into the different immunologic criteria for your SLE. I'll go back to this slide in a short while. Now when it comes to your laboratory diagnosis, there are various ways on how we can diagnose your SLE so we can quantify your complement protein specifically your C3. So C3 is the most commonly measured complement protein. So when it comes to your C3, we can quantify the levels of your C3 and associate that with your SLE. But most importantly, a more specific test for your SLE will be the detection or the presence of anti-nuclear antibody or we call this your ANA. Your ANA are group of antibodies that are usually being identified or being detected among patient with SLE. Aside from antibodies, we can also see the presence of your LE cells or your lupus erithematosus cell. So your LE cells are your polymorphonuclear cells. These are your neutrophils and sometimes even your macrophages that has an ingested LE body and often has aeroset formation. So to talk about your laboratory diagnosis for your systemic lupus erithematosus, let's start off with the presence of LE cells. So hematologically, when you see your CBC, your peripheral blood smear, you can observe your LE cells. Your LE cells again is your lupus erithematosus cell. So your LE cells are also known as your hardgrave cell. These are neutrophils or macrophages that has engulf or phagocetize at the natured nuclear material of another cell. So why do they have bakase? Bakit bakase sila merong the natured nuclear material? So take for example, there are cells that has the natured nuclear material. It is because of the presence again of your anti-nuclear antibody. So there are ANA present in your patient. That's why the nuclear material of other cells are being denatured. Now this denatured nuclear material of other cell when engulfed by your neutrophil and your macrophage would present itself in a rosette formation like this one on your screen right now. And these are now the cells which we call your lupus erithematosus or your LE cells or hardgrave cell. Now sir, ibig sabihin, meaning to say, the reason why we have LE cell is because of the anti-nuclear antibody that denatured the nuclear materials of other cell. That's very correct. As I mentioned a while back, the presence of your ANA or your anti-nuclear antibodies is the epitome or is the preferred test in diagnosing your systemic lupus erithematosus. Now let's talk about your ANA or your anti-nuclear antibodies now. So your ANA or your anti-nuclear antibodies, these are auto-antibodies that are directed against antigen in the nuclei of mammalian cells, specifically us humans. Now because of these auto-antibodies, your ANA, they specifically attack the nuclei of our mammalian cell. That's why there are denatured nuclear material that our neutrophil and macrophages engulf, hence the formation now of your LE cells. Now because of this ANA, these nuclei or the nuclear materials are being denatured. And for a fact now, your ANA or your anti-nuclear antibody are the major marker for the disease, specifically for your SLE, your rheumatoid arthritis, and even your wedger nerves granulomatosis. Sir, if you say major marker for the disease, I am actually pertaining to the systemic autoimmune diseases. Why? Because these anti-nuclear antibodies are not specific. Not specific in a sense that your rheumatoid arthritis also has a presence of ANA, your other systemic autoimmune diseases. They do have a presence of anti-nuclear antibody. So these anti-nuclear antibodies, again, they target the nuclei of your mammalian cell, the nuclear material of our cells specifically. They can attack the double-stranded or the single-stranded DNA, your histones, the proteins in which your DNA are called, your nucleosomes. These are now the complex of your DNA and histones, your centromere proteins, and even your extractable nuclear antigen or your ANA. Your extractable nuclear antigen such as your ribonucleoprotein, your SM antigen or your Smith antigen, your SSARO antigen, your SSB slash LA antigen, your SCL70, J01, and your PM1. These are examples of extractable nuclear antigen. Now, patients or I just want to be clear people, patients with SLE and rheumatoid arthritis can produce, and we do have autoantibodies that target these compounds or these molecules that are usually found in the nuclei of our mammalian cell. Again, do not get confused with ENA. ENA, these are the antigens, a group of nuclear antigens that are found inside our nucleus. Now, we have anti-nuclear antibody that can be directed against your ENA, against your DNA, your histones, your nucleosomes, or can also be for your centromere proteins. Now, since we all know that, okay, the presence of your anti-nuclear antibody pala is a marker, a major marker for your SLE. How do we detect your ENA now? Now, there are various methods on ENA detection. The first one that we're going to talk about for today is your FANA, okay? Your FANA or your Fluorescent Antinuclear Antibody. Again, your FANA or your FANA test, or your FANA testing, or your Fluorescent Antinuclear Antibody. Aside from your FANA, we also have your MIA or your MicroSphere Multiplex Immunoase. We can also use your immunofluorescence, your outstrelomy test. So, most of the tests that we're going to talk about will be mentioned later on. But again, let me just remind you that the most common test being used is your FANA, okay? Or your FNA, okay, your Fluorescent Antinuclear Antibody test. So, it is a type of an indirect immunofluorescence test, okay? Which is most widely used and accepted test in the diagnosis of your systemic lupus, erythematosis, or in general, in the detection of your ENA or your anti-nuclear antibody. So, it uses your human epithelial cell lines, specifically your hep 2 cells, which is the standard substrate for this particular test, okay? So, your Fluorescent Antinuclear Antibody test is widely used in the laboratory because it's inexpensive and it is easy to perform, okay? It is easy to perform. Now, as you can see on your screen right now, on to your right, we have a slide. And on this slide is a fixated, we have a human epithelial cell line fixed to this slide. And this specific cell line is your hep 2 cells, okay? Your hep 2 cells is the source of your nuclear antigens, okay? What nuclear antigens again, like what I have mentioned kanina, the hep 2 cells, okay? The hep 2 cells that is fixed on the slide contains your double-stranded DNA, your single-stranded DNA. In short, it contains the target of the different anti-nuclear antibody. So now that we have the substrate or we have the hep 2 cell line fixed on the slide, we would now apply your patient serum. In your patient serum, specifically take for example, your patient has your SLE. They would have antibody, okay? They would have antibody specifically, your anti-nuclear antibody. Now, if your patient has SLE, they would have ANA. And these ANA will be the one that would react to your, or would bind to the, to the hep 2 cells on your slide, okay? Okay, so let me just translate that in Tagalog. Dahil na meron tang hep 2 cells na nakafix on your, fix on your slide, the antibody, okay, the ANA from your patient sample will now bind with your cell, okay? Specifically to the different targets that we mentioned kanina, the DNA, the histones, the nucleosomes, the centromere or the extractable nuclear antigens. Now, how do we, how are we able to identify if there is a binding that happened? We apply now a anti-ANA, okay? Anti-ANA, what do you mean by anti-ANA? These are antibody directed against the anti-nuclear antibody of the patient. Now, these anti-ANA has label. So again, the label specifically for this test are fluorescent, fluorescent, fluorescent labels, okay? They are fluorescent labels. Remember, when we talk about your hypersensitivity, we have your RAS and we have your RIS. The label used there are radioactive label. Here, the one used this time are your fluorescent label. And the intensity, okay? The intensity of the intensity and the pattern, okay? The intensity and the pattern of your fluorescence will now be determined and we will be able to identify what specific ANA is present, okay? So, having said that, let's just repeat, huh? Let's just a quick review. In your slide, you have your HEP2 cell lines. They contain the nuclear antigen in which your ANA would react to. Now, if your patient has ANA, it would react to your HEP2 cell line and for us to be able to visualize that, we will be using an anti-ANA with a fluorescent label, okay? Your fluorescent label. How are we able to interpret the test, okay? So, I'll just show you an example of a result. So, as you can see, this is a result of your F, your FANA, okay? Your fluorescent anti-nuclear antibody test, okay? So, as you can see, there are different patterns and what is the significance of these patterns, okay? These patterns, okay, correspond to a specific anti-nuclear antibody. Sa madaling sabi, kapag ganito ang ityura ng ating FANA or na ng ating results, it means that this corresponds to a specific anti-nuclear antibody. But before we go to that, what are the different nuclear patterns ba, okay? What are the different nuclear patterns? So, there are various nuclear patterns that we can observe when it comes to your FANA. So, there are different patterns. It can be homogenous or diffuse. So, meaning to say, it is uniform stain or rather the entire nucleus is fluorescing, meaning to say, homogenous shall diffuse. So, this is how it looks like. The entire nucleus are fluorescing. Now, there can also be a fluorescence on the rim of the nucleus, which we call your peripheral. In your peripheral, diffuse is staining throughout the nucleus, but with greater intensity around the outer circle surrounding the nucleus. So, meaning to say, it's just the peripheral of the nucleus, okay? Second, it can also be speckled. In speckled, these are discrete fluorescent specks throughout the nucleus. These are tiny speckled all throughout your nucleus. Aside from a speckled pattern, it can also be a nuclear pattern. Nuclear pattern has a prominent staining of your nuclei. And finally, we also have your centromere pattern, where you can see numerose discrete speckled RC. Now, if you're going to differentiate your speckled pattern from your centromere pattern, the speckled pattern are more discrete, okay? They are discrete and they are bigger compared to your centromere, okay? Remember, your centromere is just an organelle of the cell. They are generally smaller. So, when you see a centromere, smaller dots or smaller dots on the nuclear pattern, then that would mean that it is a centromere pattern, okay? So now, let us just try to encapsulate what we have been talking. Now, again, let me just reiterate. In SLE, our patient has anti-nuclear antibody. And these anti-nuclear antibodies are directed against the nucleus of our cells. They can attack or they can bind to your DNA, your histones, nucleosome, centromere, or they can bind to your extractable nuclear antigen, such as the following. Now, how do we identify that? We, the most commonly used test is your FANA, okay? Now, okay, that we have discussed your FANA, how can we identify? Sir, how would we know if these anti-nuclear antibodies are double-stranded, double-stranded DNA, anti-DSDNA, or are they anti-single-stranded DNA or antibody against histone? How? We study the nuclear pattern, okay? We study the nuclear pattern. So again, this is a homogenous pattern. So as you can see, the entire nucleus is, the entire nucleus is fluorescing. So the fluorescence there, meaning to say, those are the antibody press that has bind to the nucleus. We also have your nuclear pattern, okay? Nuclear patterns, as you can see, they are big enough. Big, malalaki sila, okay? It binds to the nucleoli of the cell. And we also have your speckled, and this is your speckled pattern, okay? So how does it happen? So in your cell, in your slide, rather, we have your slides. So take, for example, each slide, your slide meron kang 1, 2, 3, 4, 5, 6. So these six wells here, okay? The six wells that you can see here, guys, these are all HEP2 cells, okay? HEP2 cells or your epithelial cell line. So you drop your antibody, you drop your serum here, you drop your serum here, here, here, here, and here. Now, you allow your patient serum to incubate with the slide, and then if there is presence of anti-nuclear antibody, they would bind to your nucleus. Again, in different patterns. Some homogenous, it can also be speckled, some are peripheral, some are nuclear. Now, first of all, to visualize that, what are we going to add? We are going to add an anti-ANA, anti-ANA with fluorescent label. That's why we're able to visualize. Okay, it's homogenous. Okay, it's speckled. Okay, the pattern is peripheral. Okay, the pattern is nuclear. Now, the bigger question now is that, what does this pattern signifies? Okay? What does this pattern signifies? On table 15-2 of your chapter 15 in your book, you can see the different auto-antibody. So, you have your anti-DSDNA. That means it is an anti-double-stranded DNA, anti-single-stranded DNA, anti-histone, anti-DNP, or deoxynocleoprotein, your anti-SM or your anti-Smith, which is an example of an extractable nuclear antigen, your anti-RNP. Okay? You also have here your RNP or your ribonucleoprotein, your anti-SSA, RO, and other auto-antibody. Now, since we're talking about systemic lupus erithematosus, it's very important for you to familiarize yourself. Sir, how do we memorize or how do we study the table? Of course, number one, you study the auto-antibody. Okay? What are the different auto-antibody? I think we mentioned this kanina, the different anti... This auto-antibody, these are your anti-nuclear antibody. Okay? So, characteristic antigen, as you can see, they are directed against the double-stranded DNA. Okay? So, what are their pattern? This is important. Okay? If the pattern is peripheral or the pattern is homogenous, that means that the one you see are DSDNA. So, let's go back. If you see this pattern, oh, this is homogenous. Okay? The pattern is homogenous, meaning to say the antibody that is present are anti-DSDNA or anti-double-stranded DNA. Antibodies directed against the double-stranded DNA of the cell. Okay? That's how you study that or that's how you study this table. Okay? It's important for you to remember the immunofluorescent pattern. Now, what about for SLE? What are the auto-antibody? What are the anti-nuclear antibodies that are specific to SLE? Just like what I mentioned kanina, your ANA are nonspecific, but with knowing the correct, I mean, the correct nuclear pattern you're able to identify which one are specific for SLE. Those are your anti-DSDNA. Okay? And your auto-antibody against your anti-centromere. Okay? As you can see here, guys, your anti-DSDNA is specific for SLE. Your anti-smith is also a diagnostic for SLE. Your auto-antibody or your anti-centromere is also specific for your crest syndrome, specifically your calcinosis, reinoids phenomenon, isofagyl dysmotility, scleral ductility, and telanggeksha. Okay? Telanggeksha. So, these are also system. These are now a combination of different diseases. Okay? Now, identified as also your SLE. Now, as you can see here, your DSDNA, peripheral and homogenous. If you see peripheral and homogenous, it means that it is for your SLE. Okay? It means that it has the presence of anti-DSDNA specific for SLE. If you observe course speckled, okay? Course speckled, then that would mean, okay, that that is for your SLE. Okay? If presence of anti-smith, the anti-DSDNA, all specific for SLE. As you can see, the other anti-nuclear antibody, presence ya sa SLE. Yes, it is present in your SLE, but it can also be seen in other diseases. That's why if you're going to look at a specific laboratory result, even if you see that there's presence of anti-single-stranded DNA, presence of anti-histone, you always look at the DSDNA and your anti-smith, just for you to be able to make sure that it is indeed SLE. As you can see, I also want you guys to take note. You also have here drug-induced SLE. You can see anti-histone, anti-DNP. Okay? And as you can see, other anti-nuclear antibody are also present in other diseases. That's why again, ha, it's important for you to remember anti-DSDNA and anti-smith and also your anti-centromere. So again, that is your fluorescent anti-nuclear antibody test. Okay? So with the different two clear patterns, we're able to identify the specific auto-antibody. Now, moving forward, okay? Hopefully, we understood how we interpret. So again, if you see these patterns, okay? If you see these patterns in your FANA test, you would know, okay? What are the specific anti-nuclear antibody tests? What are the specific anti-nuclear antibody that they represent? Okay? So aside from FANA, okay? This part now will just be a quick run-through of the different tests that can be used to identify your anti-nuclear antibody. So FANA test is just one, okay? We just spent more time there because it is the most commonly used in that laboratory. But aside from FANA, it uses a micro-titer plate containing a suspension of your polystyrene micro-spear that are coated with individual nuclear antigen or with hep 2 extra. So kanina, we have a slide in which we have a fixed hep 2 cells on those specific slide. Here, what we have are micro-titer plate. So we have a well and on the well, we have the specific nuclear antigens na mismo na fixed on the web. So instead of having different patterns to study in your micro-spear multiplex immunosasate, you can simply just see, okay, in which specific well your patient serum reacted. It's more similar with your RAS, your radio-electrosorbentase. They're already specific allergen on the well, di ba? Here, there's already a specific nuclear antigen in the well. And you can simply identify what specific antibody is present based on the result. So the antibody in your present will bind only to the bead containing a specified antigen. Like, for example, you have a well that contains your DSDNA. If the antibody reacted to that, you would see a positive result on that particular well. Okay, so similarly, we are using a anti-human IgG. So meaning to say, another antibody directed against your anti-nuclear antigen, rather anti-nuclear antibody. So the bead suspension is analyzed for fluorescence. So if they, for example, there's fluorescence in the particular well that contains your DSDNA, that would mean that your patient has anti-DSDNA. Okay, so one that identifies each bead and the other that detects the amount of fluorescence conjugate attach. Okay, so again, it's very, your MIA is very similar with your RAS. It has a specific nuclear antigen in each well. So once your anti-nuclear antigen or anti-nuclear antibody bind to that, you'll be able to identify what specific ANA is present. Okay, so aside from FANA, we have your MIA or your microsphere multiplex immunoassay. We also have your immunofluorescence using your Chrithidia lucilia. So I want you guys to remember your Chrithidia lucilia. Your Chrithidia lucilia is a trepanosol that has a circular organelle, that is mainly composed of your double-stranded DNA. That's why, okay, remember that the Chrithidia lucilia will fluoresce when your DSDNA bind to that. So how do we do your immunofluorescence using your Chrithidia lucilia? So we have your trepanosol. We have your Chrithidia lucilia and then we allow our patients to react with this organism or this trepanosol. Specifically, the Chrithidia lucilia only contains double-stranded DNA. It contains double-stranded DNA. Now, because it contains double-stranded DNA, remember, your anti-DSDNA is a diagnostic marker for your SLE. Meaning to say, if your antibody or the anti-nuclear antibody of your patient reacted with your Chrithidia lucilia or your trepanosol, it means that the patient has anti-DSDNA. And because of that, sir, how are we going to visualize that? Again, we use, okay, we also use here an anti-NA that has a fluorescent label. Okay? So if your antibody to DSDNA is present, you would see your Chrithidia lucilia fluorescing. So if you do not have, okay, if the Chrithidia lucilia is negative or it doesn't fluoresce, meaning to say, your patient doesn't have DSDNA. So most probably it is a different anti-nuclear antibody or it is negative to SLE in short. Okay? So again ha, ang ating Chrithidia lucilia mag-fluofluoresc lang kapag-present ang anti-DSDNA. Okay? So again, that is for your immunofluorescence using your Chrithidia lucilia. Aside from that, we also have your outstir-lowny test. So no need to bother when it comes to outstir-lowny test because we will be discussing this when we go to your immunodefusion in the semifinals. So your outstir-lowny test is a type of immunodefusion test used to determine an immunologic specificity of your positive FANA. So take for example you have this is usually done if you guys could observe no, there are some anti-nuclear antibody with the same immunofluorescent pattern or nuclear pattern. Like take for example, a lot of these are homogenous, a lot of them are speckled. So for you to be able to identify what specific anti-nuclear antibody is that okay after FANA, okay after your fluorescent anti-nuclear antibody test, you proceed with outstir-lowny test. In your outstir-lowny test we are able to identify the identity of your antibody. Okay, so you can identify your Smith, your RNP, your SSA, your SSB, your SCL70 and your J01. Again, that is your outstir-lowny test. Your outstir-lowny test is used to identify the specific specific anti-nuclear antibody present in your patient. Because again your DSDNA di ba? Kita mo naman pag-periferal or homogenous that's only for DSDNA. But for others, like your Smith, your RNP both are coarsely speckled in your SSA, SSB how are you going to differentiate one from the other? You see both of them are finely speckled. Again, what you do is perform your outstir-lowny test. Again, perform your outstir-lowny test. Now, aside from the presence of your anti-nuclear antibody, so those are the procedure or those are the methods on how we identify your anti-nuclear antibody. Again, we have your FANA, we have your MIA or your microspear multiplex immunoassay and we also have the immunofluorescence test using your Crithidialusilane and of course your outstir-lowny test. Now, aside from your anti-nuclear antibodies what else can we observe in patient with SLE? We also have presence of your antifospholipid antibody. Your antifospholipid antibody are antibodies that bind to your phospholipid alone or the phospholipid complex with protein. Although the problem with your antifospholipid antibody is it is also non-specific. In a sense that your antifospholipid antibody can also be identified in other diseases like syphilis, syphilis, even your rheumatoid arthritis, you can also observe presence of antifospholipid antibody. But why are we using antifospholipid antibody? Antifospholipid antibody can serve as a screening test in many levels. So take for example, you tested positive for antifospholipid antibody. Usually we would suspect syphilis. Okay? You would suspect syphilis. But if the patient is negative for syphilis then that would now alert your doctor that they need to perform series of tests to identify are these antifospholipid antibody because of syphilis or because of lupus or because of other autoimmune diseases. Okay? So aside from antifospholipid antibody what else can we observe in patient? Okay? What laboratory test or laboratory result can we still observe in patient with SLE? We can also observe the presence of your lupus anticoagulant. If you are in my class in hematology 2, we have mentioned your lupus anticoagulant last meeting. So in your lupus anticoagulant remember both your pro time or rather your pro thrombin time baka di kayo familiar sa pro time your pro time or your pro thrombin time and your activated partial thromboclastin are both both increase or both prolong. Now how are we able to identify if these are coagulation factory deficiency? When you perform your substitution study which I will be discussing to you guys this week on Thursday or Friday depending on your section we will be discussing how do we identify lupus anticoagulant. So again with respect to immunology with respect to SLE patient with systemic lupus eritimatosis has your lupus anticoagulant. So there are two markers in HEMA that we can observe the presence of your LES cells and the presence of your lupus anticoagulant. Again how do we identify the presence of your lupus anticoagulant? Both your PT and PTT are increased. Is it just a matter of coagulation factor deficiency that belongs to the common pathway? Your analogy or your analysis is partly correct. But again when we perform your substitution studies again to be discussed this coming Thursday and Friday you would observe that it is not corrected. So with lupus anticoagulant it increase the risk of clotting and patient in women it increases the possibility of spontaneous abortion. So again presence of lupus anticoagulant is observed in patients with SLE together with the presence of antifospholipid antibody and of course the marker for your SLE is the presence of your anti-nuclear antibody. Now which leads us now to the criteria for your SLE. The different criteria for your SLE can be clinical, the different symptoms or it can also be immunologic. Again elevated ANA now since we're talking about ANA there are a lot of anti-nuclear antibody there are two specific anti-nuclear antibody that are marker for SLE that is elevated DSDNA. So meaning to say when you do your FANA there is a fluorescence or homogenous or peripheral nuclear pattern. You're also presence of your anti-smith antibody. Again when you perform your FANA you still need to do your outstriolomy test to identify the presence of your anti-smith. There's also the presence of anti-phospholipid antibody although not specific for SLE but you can observe that low complement protein low complement protein specifically low C3 levels and of course positive that in the absence of hemolytic anemia. Now always remember that according to the systemic lupus international collaborating clinics a patient must satisfy at least four of this clinical and immunologic criterion for them to be declared or for them to be diagnosed with SLE. Again four out of the 17 at least okay at least four out of the 17 17 criterion okay four out of the 17 criteria so kung meron tang present ng apat na to out of 17 then that could be declared as systemic lupus erythematosus okay so I hope that's clear everyone so we talk about your systemic lupus erythematosus for our next meeting we will be talking about your we'll be talking about your rheumatitis and other organ specific autoimmune diseases. For now thank you so much for listening so that is it for today thank you so much and I will see you on our next synchronous class this week okay thank you so much and have a great day.