This article was truly fascinating to me on a personal level. I have a vested interest in this disease and more importantly in its cure due to a possible genetic predisposition that runs in my family and maybe even dormant in me. So, needless to say, I am intrigued.
The article specifically focuses on the formation of the senile plaques and the inflammatory events that are included therein. I supplemented my own understanding of the disease and insight into the article with www.alz.org. This was very helpful, particularly the pictures and interactive parts.
It is clear that the senile plaques are perhaps the most important thing for diagnosis and the destructive nature of the disease, but the article didn't really address another key pathology: the neurofibrillatory tangles. It is mentioned in the introduction, and in the summary, but the article fails to address this issue at all, really. My own investigation on a few good sites illuminated this a little for me. The tangles are torsions of a specific protein, called tau, that sort of "links" and "organizes" a track-like protein network used in nutrient and food-molecule delivery. The carefully organized system is like parallel rows of train tracks, and this twisted tau protein unaligns the rows and ends up in a loss of this vital network. This is a major component of the loss of the brain cells and tissue which causes the devastating disease.
Obviously the Beta-Amyloid plaques are a crucial element, and there is plenty of inflammatory involvement in this process of degradation, but there may also be a correlation to this other protein-linked event that is a primary factor.
01 November 2007
IgG as anti inflammatory
Hey eveyone,
This post is in regard to what Prof. Cohen mentioned in class on Tuesday regarding IgG as an anti-inflammatory. I'm curious to know more about this. I did a study on morphine last year, learning how continuous doses of morphine causes tolerance, and (believe it our not) more pain. When injected intrathecally, morphine attaches to TLR-4 receptors on glia in the spinal cord. Glia then release IL-1, causing inflammation, which inhibits the analgesic properties of morphine acting on neurons. If you co-administer an anti-inflammatory like IL-10 with morphine, analgesia increases. It's bizzare to think that morphine can cause more pain when used chronically.
Anyway, what I'm curious about is the role IgG plays (ie the mechanism) in having anti-inflammatory effects. I'm wondering if an endogenous substance of the body (IgG), when injected and used as an anti-inflammatory, can cause tolerance, or resistance, similar to the type of tolerance caused by chronic morphine.
In a sense, my question is could our bodies become immune to the anti-inflammatory effects of IgG, if it is used over long periods of time?
I need to look into this still...I just needed to type this while its fresh on my mind.
A reference:
Norman Cousins Lecture. Glia as the "bad guys": implications for improving clinical pain control and the clinical utility of opioids.
Watkins LR, Hutchinson MR, Ledeboer A, Wieseler-Frank J, Milligan ED, Maier SF
Brain Behav Immun. 2007 Feb;21(2):131-46. Epub 2006 Dec 18
Chris Altmann
This post is in regard to what Prof. Cohen mentioned in class on Tuesday regarding IgG as an anti-inflammatory. I'm curious to know more about this. I did a study on morphine last year, learning how continuous doses of morphine causes tolerance, and (believe it our not) more pain. When injected intrathecally, morphine attaches to TLR-4 receptors on glia in the spinal cord. Glia then release IL-1, causing inflammation, which inhibits the analgesic properties of morphine acting on neurons. If you co-administer an anti-inflammatory like IL-10 with morphine, analgesia increases. It's bizzare to think that morphine can cause more pain when used chronically.
Anyway, what I'm curious about is the role IgG plays (ie the mechanism) in having anti-inflammatory effects. I'm wondering if an endogenous substance of the body (IgG), when injected and used as an anti-inflammatory, can cause tolerance, or resistance, similar to the type of tolerance caused by chronic morphine.
In a sense, my question is could our bodies become immune to the anti-inflammatory effects of IgG, if it is used over long periods of time?
I need to look into this still...I just needed to type this while its fresh on my mind.
A reference:
Norman Cousins Lecture. Glia as the "bad guys": implications for improving clinical pain control and the clinical utility of opioids.
Watkins LR, Hutchinson MR, Ledeboer A, Wieseler-Frank J, Milligan ED, Maier SF
Brain Behav Immun. 2007 Feb;21(2):131-46. Epub 2006 Dec 18
Chris Altmann
Enzyme-Linked ImmunoSpot (ELISPOT) Assay
The Cytokine Enzyme-Linked ImmunoSpot (ELISPOT) Assay: Potential New Technology for Diagnosis and Studying Immune Function in Disease States
In certain disease processes, particularly those directly involving a cell-mediated immune response, the ability to study the function of T-cells and the cytokine products they secrete in response to specific antigen stimulation (for instance, a type 1 diabetes auto-antigen or a Mycobacterium tuberculosis antigen) can provide useful information about immune function and disease state. T-cells, based upon the cytokines they happen to be secreting, tell a tale of disease state (in the case of type 1 diabetes and other autoimmune disorders) or indicate presence of memory T-cells specific to exposure to antigen (in the case of Mycobacterium tuberculosis antigen), useful in diagnosing a particular condition.
The cytokine ELISPOT assay is relatively new technology currently being developed for studying T-cell and immune function that may, in the near future, be available for physicians as a diagnostic tool. It is based upon a modified version of the popular Enzyme-Linked ImmunoSorbent Assay (ELISA) and allows for the identification and enumeration of cytokine-producing cells at the single cell level. Simply put, at appropriate conditions, the ELISPOT assay allows visualization of the secreted product (cytokines) of individual activated T-cells to a specific peptide antigen. How do you “see” what cytokines individual T-cells are producing? You incubate T-cells with an antigen of interest, during which the stimulated T-cells will release cytokine in response to antigen. You then transfer the T-cells to another culture dish that has anti-cytokine antibody stuck to it (similar method to the ELISA) and the culture is allowed to sit. The T-cells are lysed, washed away, and individual spots appear after treatment with chemicals (similar to those used in photography to develop a photo) that specifically make the spots appear dark brown. Each spot that develops in the assay represents a single cell that has reacted to your chosen peptide antigen and has secreted cytokine in response to stimulation by peptide. Thus, the ELISPOT assay provides exquisitely sensitive qualitative (type of cytokine – many different anti-cytokine antibodies are available) and quantitative (number of responding cells) information (1).
Based upon relative secretion of different cytokines, the ELISPOT assay is an effective tool to enumerate T-cells with either a Th1 or Th2 phenotype and observe for more of a tendency toward a Th1 or Th2 immune response. For instance, you might stick anti-IL-10 antibody to a culture plate to capture a Th2 response, and you might stick anti-interferon gamma antibody to capture a Th1 response and compare the response of the same population of cells to the two different cytokines. This is useful in patients with an autoimmune disease, such as type 1 diabetes, and makes it possible to characterize disease state at a more detailed level. Studies have shown that those who have or who are genetically “at risk” for developing type 1 diabetes will often exhibit more of a Th1 response to diabetes auto-antigens relative to a Th2 response (2). While the assay is still under experimental development for use as a diagnostic aid, the results are promising for use as a clinical indicator of possible type 1 diabetes detectable much sooner than any clinical method we currently have available (5).
ELISPOT technology is also currently being developed to detect latent and active Tuberculosis infections. Diagnosis and preventative treatment of people with early tuberculosis infection before they develop disease (active tuberculosis) is a crucial element of tuberculosis control (4). Often the standard test for TB exposure (PPD test) gives false positives and false negatives (3), and ELISPOT technology would allow for more accurate determination of Mycobacterium tuberculosis exposure by detecting T cells responding to ESAT-6, a protein expressed in the tuberculosis bacterium, but absent from all strains of BCG vaccine (TB vaccine). These T-cells, if present, will secrete interferon gamma in response to antigen, and this interferon gamma can be detected.
ELISPOT technology has many, many more potentially clinically useful applications and may be uniquely useful for monitoring antigen-specific responses applicable to a wide range of areas in immunology research, including cancer, transplantation, infectious disease, and vaccine development.
References:
1.) http://en.wikipedia.org/wiki/ELISPOT
2.) Schloot, N. et al. 2003. Comparison of cytokine ELISPOT assay formats for the detection of islet antigen autoreactive T-cells. Journal of Autoimmunity: 21 (2203) 365 – 367.
3.) Booth, H. 2004. How tuberculosis can be diagnosed. The Pharmaceutical Journal: 273
4.http://www.brightsurf.com/news/headlines/17092/ACCURATE_IDENTIFICATION_OF_EARLY_TUBERCULOSIS_INFECTION_POSSIBLE_WITH_NEW_BLOOD_TESTp_2017.html
5.) Roep, B. et al. 1999. Autoreactive T cell Responses in Insulin-Dependent (Type 1) Diabetes Mellitus. Journal of Autoimmunity: 13, 267 – 282
In certain disease processes, particularly those directly involving a cell-mediated immune response, the ability to study the function of T-cells and the cytokine products they secrete in response to specific antigen stimulation (for instance, a type 1 diabetes auto-antigen or a Mycobacterium tuberculosis antigen) can provide useful information about immune function and disease state. T-cells, based upon the cytokines they happen to be secreting, tell a tale of disease state (in the case of type 1 diabetes and other autoimmune disorders) or indicate presence of memory T-cells specific to exposure to antigen (in the case of Mycobacterium tuberculosis antigen), useful in diagnosing a particular condition.
The cytokine ELISPOT assay is relatively new technology currently being developed for studying T-cell and immune function that may, in the near future, be available for physicians as a diagnostic tool. It is based upon a modified version of the popular Enzyme-Linked ImmunoSorbent Assay (ELISA) and allows for the identification and enumeration of cytokine-producing cells at the single cell level. Simply put, at appropriate conditions, the ELISPOT assay allows visualization of the secreted product (cytokines) of individual activated T-cells to a specific peptide antigen. How do you “see” what cytokines individual T-cells are producing? You incubate T-cells with an antigen of interest, during which the stimulated T-cells will release cytokine in response to antigen. You then transfer the T-cells to another culture dish that has anti-cytokine antibody stuck to it (similar method to the ELISA) and the culture is allowed to sit. The T-cells are lysed, washed away, and individual spots appear after treatment with chemicals (similar to those used in photography to develop a photo) that specifically make the spots appear dark brown. Each spot that develops in the assay represents a single cell that has reacted to your chosen peptide antigen and has secreted cytokine in response to stimulation by peptide. Thus, the ELISPOT assay provides exquisitely sensitive qualitative (type of cytokine – many different anti-cytokine antibodies are available) and quantitative (number of responding cells) information (1).
Based upon relative secretion of different cytokines, the ELISPOT assay is an effective tool to enumerate T-cells with either a Th1 or Th2 phenotype and observe for more of a tendency toward a Th1 or Th2 immune response. For instance, you might stick anti-IL-10 antibody to a culture plate to capture a Th2 response, and you might stick anti-interferon gamma antibody to capture a Th1 response and compare the response of the same population of cells to the two different cytokines. This is useful in patients with an autoimmune disease, such as type 1 diabetes, and makes it possible to characterize disease state at a more detailed level. Studies have shown that those who have or who are genetically “at risk” for developing type 1 diabetes will often exhibit more of a Th1 response to diabetes auto-antigens relative to a Th2 response (2). While the assay is still under experimental development for use as a diagnostic aid, the results are promising for use as a clinical indicator of possible type 1 diabetes detectable much sooner than any clinical method we currently have available (5).
ELISPOT technology is also currently being developed to detect latent and active Tuberculosis infections. Diagnosis and preventative treatment of people with early tuberculosis infection before they develop disease (active tuberculosis) is a crucial element of tuberculosis control (4). Often the standard test for TB exposure (PPD test) gives false positives and false negatives (3), and ELISPOT technology would allow for more accurate determination of Mycobacterium tuberculosis exposure by detecting T cells responding to ESAT-6, a protein expressed in the tuberculosis bacterium, but absent from all strains of BCG vaccine (TB vaccine). These T-cells, if present, will secrete interferon gamma in response to antigen, and this interferon gamma can be detected.
ELISPOT technology has many, many more potentially clinically useful applications and may be uniquely useful for monitoring antigen-specific responses applicable to a wide range of areas in immunology research, including cancer, transplantation, infectious disease, and vaccine development.
References:
1.) http://en.wikipedia.org/wiki/ELISPOT
2.) Schloot, N. et al. 2003. Comparison of cytokine ELISPOT assay formats for the detection of islet antigen autoreactive T-cells. Journal of Autoimmunity: 21 (2203) 365 – 367.
3.) Booth, H. 2004. How tuberculosis can be diagnosed. The Pharmaceutical Journal: 273
4.http://www.brightsurf.com/news/headlines/17092/ACCURATE_IDENTIFICATION_OF_EARLY_TUBERCULOSIS_INFECTION_POSSIBLE_WITH_NEW_BLOOD_TESTp_2017.html
5.) Roep, B. et al. 1999. Autoreactive T cell Responses in Insulin-Dependent (Type 1) Diabetes Mellitus. Journal of Autoimmunity: 13, 267 – 282
Inflammation in Multiple Sclerosis
The review by Martino et al mentioned various forms of Multiple Sclerosis (MS) without any real description or delineation of the disease types. Patients who suffer from MS are diagnosed with one of four forms of the disease.
1. Relapsing-Remitting (85% of patients are diagnosed with this form of the disease) In this form, patients exhibit clearly defined flare-ups (relapsing stages of inflammation) followed by clearly defined remissions (inflammation subsides). In between relapses and remissions, patients report feeling "disease free."
2. Primary Progressive (10% of patients) Patients with this form of MS exhibit a slow, continuous worsening of their disease without clearly defined relapses and remissions.
3. Secondary Progressive (50 % of Relapsing-Remitting patients will deteriorate into this form of MS within 10 years of their initial diagnosis) This form is characterized by the initial relapsing-remitting state of MS followed by a steady decline in the health of the CNS. Secondary Progressive MS differs from Primary Progressive in that patients may experience small remissions in their condition.
4. Progressive-Relapsing (5% of patients) Progressive-Relapsing MS is defined by a continual worsening of the disease with obvious acute relapsing phases.
The various types and progressions of MS seem to be indicative of different pathologies of inflammation. What is static between all four forms of the disease is the fact that immune cells are attacking the oligodendrocytes within the CNS and the Schwann cells in the PNS that are responsible for myelination of the nervous system. Furthermore, gadolinium (the contrast used in MRI imaging of the disease) may enhanced MS inflammatory episodes, initiating more lesions to form in the nervous system. These factors make it necessary for therapies to be created to treat each form of MS as most treatments now only treat relapsing forms of the disease (only when diagnosed early enough).
There is a drug on the market currently for Relapsing-Remitting MS called Tysabri. This drug is a monoclonal antibody which deters immune cells, which may be detrimental to the nervous system, from entering the blood stream, and eventually the blood brain barrier. Patients receiving this treatment experience fewer relapses. This drug was temporarily removed from the market as several patients contracted a rare, fatal brain disease called leukoencephalopathy. After reconsideration by the FDA, Tysabri was re-released with new guidelines.
Tysabri has not been tested on the other three forms of MS, but as it possibly prevents damaging immune cells from entering the blood brain barrier and the CSF it may be a new good avenue of research.
Mayo Clinic. "Multiple Sclerosis: Treatment." 6 Dec. 2006. http://www.mayoclinic.com/health/multiple-sclerosis/DS00188/DSECTION=7
National Multiple Sclerosis Society. "Tysabri (Natalizumab)." 9 Oct. 2007. http://www.nationalmssociety.org/site/PageServer?pagename=HOM_LIVE_meds_natalizumab
National Multiple Sclerosis Society. "What is Multiple Sclerosis". 3 Aug. 2006. http://www.nationalmssociety.org/site/PageServer?pagename=HOM_ABOUT_what_is_ms
1. Relapsing-Remitting (85% of patients are diagnosed with this form of the disease) In this form, patients exhibit clearly defined flare-ups (relapsing stages of inflammation) followed by clearly defined remissions (inflammation subsides). In between relapses and remissions, patients report feeling "disease free."
2. Primary Progressive (10% of patients) Patients with this form of MS exhibit a slow, continuous worsening of their disease without clearly defined relapses and remissions.
3. Secondary Progressive (50 % of Relapsing-Remitting patients will deteriorate into this form of MS within 10 years of their initial diagnosis) This form is characterized by the initial relapsing-remitting state of MS followed by a steady decline in the health of the CNS. Secondary Progressive MS differs from Primary Progressive in that patients may experience small remissions in their condition.
4. Progressive-Relapsing (5% of patients) Progressive-Relapsing MS is defined by a continual worsening of the disease with obvious acute relapsing phases.
The various types and progressions of MS seem to be indicative of different pathologies of inflammation. What is static between all four forms of the disease is the fact that immune cells are attacking the oligodendrocytes within the CNS and the Schwann cells in the PNS that are responsible for myelination of the nervous system. Furthermore, gadolinium (the contrast used in MRI imaging of the disease) may enhanced MS inflammatory episodes, initiating more lesions to form in the nervous system. These factors make it necessary for therapies to be created to treat each form of MS as most treatments now only treat relapsing forms of the disease (only when diagnosed early enough).
There is a drug on the market currently for Relapsing-Remitting MS called Tysabri. This drug is a monoclonal antibody which deters immune cells, which may be detrimental to the nervous system, from entering the blood stream, and eventually the blood brain barrier. Patients receiving this treatment experience fewer relapses. This drug was temporarily removed from the market as several patients contracted a rare, fatal brain disease called leukoencephalopathy. After reconsideration by the FDA, Tysabri was re-released with new guidelines.
Tysabri has not been tested on the other three forms of MS, but as it possibly prevents damaging immune cells from entering the blood brain barrier and the CSF it may be a new good avenue of research.
Mayo Clinic. "Multiple Sclerosis: Treatment." 6 Dec. 2006. http://www.mayoclinic.com/health/multiple-sclerosis/DS00188/DSECTION=7
National Multiple Sclerosis Society. "Tysabri (Natalizumab)." 9 Oct. 2007. http://www.nationalmssociety.org/site/PageServer?pagename=HOM_LIVE_meds_natalizumab
National Multiple Sclerosis Society. "What is Multiple Sclerosis". 3 Aug. 2006. http://www.nationalmssociety.org/site/PageServer?pagename=HOM_ABOUT_what_is_ms
31 October 2007
Drug Induced Parkinsons Disease
After reading the article on cytokine role in the inflammatory role in Parkinson's disease I researched other causes of Parkinson's and found that in some cases Parkinson's can be drug-induced. Some anti -psychotic medications can contribute to Parkinson's because they lower the dopaminergic activity. A drug called Levadopa is most commonly used to treat Parkinson's but overtime it becomes counter productive due to feedback inhibition. This results in a disease called Levodopa (LD)-induced dyskinesia (LID) one of the most common motor complications in advanced Parkinson's disease.
Reference
Burkhard PR., Grotzch H, Sztajzel R. Levadopa - induced ocular dyskinesia in Parkinson's disease. Eur J Neurol. 2007 Oct 14(10):1124-8.
Reference
Burkhard PR., Grotzch H, Sztajzel R. Levadopa - induced ocular dyskinesia in Parkinson's disease. Eur J Neurol. 2007 Oct 14(10):1124-8.
30 October 2007
Anti-IL-17 antibody in the treatment of CIA
Many of the articles we have looked at so far concerning arthritis have discussed the role of the proinflammatory cytokines IL-1 and TNF-alpha. However, one study looked at IL-17, another proinflammatory cytokine that is expressed inthe synovium of patients with rheumatoid arthritis. The ultimate goal of the study was to identify the role of IL-17 in the effector phase of arthritis. Polyclonal anti-murine IL-17 anitbody postive serum was used to treat mice with collagen induced arthritis (CIA) after the first signs of arthrits. The control rgoup was given normal rabbit serum. Anti-IL-17 anitbody or control serum was also given to mice with later stages of CIA. The results showed that the severity of CIA was significantly reduced with anti-IL-17 antibody treatment. Joint damage was supressed in the knees and ankles of the mice, and inflammation was also supressed. More specifically, blocking of IL-17 also prevented focal bone erosion, and supressed serum IL-6 levels. A reduced number of cells expressing RANKL and IL-beta was also observed after anti-IL-17 treatment. Anti-IL-17 treatment was also effective in the later stages of CIA. The results showed that after a single injection with the anti-IL-17 antibody, the progression of the arthritis in the knee and ankle of the mice was significantly slowed. This shows that IL-17 does indeed play a role in the prolongation of arthritis. This study is important because it analyzes the role of IL-17 in arthritis as well as the relationship between IL-17 and other proinflammatory cytokines such as IL-1, TNF-alpha and IL-6, which is critical in the development of future therapies for arthritis. Overall, this study was well laid out and showed extremely promising results; however, one question that has bothered me when reading many of the articles this semester: have there been any observed side effects of these treatments? And if so, why does it seem as though adverse side effects are never discussed?
(1) Erik Lubberts, et all. Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of collagen-induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion. Arthrits and Rheumatism. 50(2) 650-659. 2004
(1) Erik Lubberts, et all. Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of collagen-induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion. Arthrits and Rheumatism. 50(2) 650-659. 2004
28 October 2007
HLA and variation in the immune response to vaccines
Human leukocyte antigen polymorphisms and variation in the immune response to vaccines.
Despite availability of effective vaccines, disease outbreaks can occur in highly vaccinated populations. For example, 20-40% of subjects in the 1989-1991 US measles outbreak had been previously immunized against measles. One of the most logical places to explain the variation in the individual response to vaccines lies within the highly polymorphic human leukocyte antigen (HLA) system. For vaccines to be immunogenic, each individual must be capable of presenting vaccine antigens bound to the specific HLA alleles carried by the individual to the T cells, thus stimulating an effective immune response to the foreign antigen. Because of this HLA-restricted antigen recognition and presentation and because of the variations in HLA distribution across populations, different vaccines may not be uniformly effective across populations.
Several genetic association population-based studies have identified associations between specific class I and II HLA alleles and the antibody response to several vaccines including Measles, Mumps, Rubella, Hepatitis B and Influenza. These associations range from ‘poor’ to ‘hyper’ humoral immune responses to vaccines. For example, Ovsyannikova et al have extensively studied the association between measles vaccine induced antibody response and HLA genes. They found that class I HLA-B alleles, including HLA-B8, HLA-B13 and HLA-B44 were associated with seronegativity, whereas alleles HLA-B7 and HLA-B51 were associated with seropositivity. Among class II alleles, seronegative individuals had an excess of HLA-DRB1*03 and HLA-DPA1*0201 alleles compared to seropositives. They also studied the associations between HLA genes and very high levels of measles antibodies (hyper-responsiveness) and found that HLA alleles B7, DQA1*0104 and DPA1*0202 were over-represented in the group of measles vaccine hyperseropositive individuals.
The effect of the HLA alleles on immune response to vaccines can have important implications in understanding vaccine immunogenicity as well as for directed vaccine development - to build cocktails of vaccine antigen epitopes that provide immunological coverage for populations by binding antigens across a diverse range of HLA types.
References:
G. A. Poland and R. M. Jacobson. Failure to reach the goal of measles elimination. Apparent paradox of measles infections in immunized persons. Archives of Internal Medicine 154 (16):1815-1820, 1994.
I. G. Ovsyannikova, N. Dhiman, R. M. Jacobson, and G. A. Poland. Human leukocyte antigen polymorphisms: variable humoral immune responses to viral vaccines. Expert Review of Vaccines 5 (1):33-43, 2006.
I. G. Ovsyannikova, R. M. Jacobson, and G. A. Poland. Variation in vaccine response in normal populations. Pharmacogenomics 5 (4):417-427, 2004.
Despite availability of effective vaccines, disease outbreaks can occur in highly vaccinated populations. For example, 20-40% of subjects in the 1989-1991 US measles outbreak had been previously immunized against measles. One of the most logical places to explain the variation in the individual response to vaccines lies within the highly polymorphic human leukocyte antigen (HLA) system. For vaccines to be immunogenic, each individual must be capable of presenting vaccine antigens bound to the specific HLA alleles carried by the individual to the T cells, thus stimulating an effective immune response to the foreign antigen. Because of this HLA-restricted antigen recognition and presentation and because of the variations in HLA distribution across populations, different vaccines may not be uniformly effective across populations.
Several genetic association population-based studies have identified associations between specific class I and II HLA alleles and the antibody response to several vaccines including Measles, Mumps, Rubella, Hepatitis B and Influenza. These associations range from ‘poor’ to ‘hyper’ humoral immune responses to vaccines. For example, Ovsyannikova et al have extensively studied the association between measles vaccine induced antibody response and HLA genes. They found that class I HLA-B alleles, including HLA-B8, HLA-B13 and HLA-B44 were associated with seronegativity, whereas alleles HLA-B7 and HLA-B51 were associated with seropositivity. Among class II alleles, seronegative individuals had an excess of HLA-DRB1*03 and HLA-DPA1*0201 alleles compared to seropositives. They also studied the associations between HLA genes and very high levels of measles antibodies (hyper-responsiveness) and found that HLA alleles B7, DQA1*0104 and DPA1*0202 were over-represented in the group of measles vaccine hyperseropositive individuals.
The effect of the HLA alleles on immune response to vaccines can have important implications in understanding vaccine immunogenicity as well as for directed vaccine development - to build cocktails of vaccine antigen epitopes that provide immunological coverage for populations by binding antigens across a diverse range of HLA types.
References:
G. A. Poland and R. M. Jacobson. Failure to reach the goal of measles elimination. Apparent paradox of measles infections in immunized persons. Archives of Internal Medicine 154 (16):1815-1820, 1994.
I. G. Ovsyannikova, N. Dhiman, R. M. Jacobson, and G. A. Poland. Human leukocyte antigen polymorphisms: variable humoral immune responses to viral vaccines. Expert Review of Vaccines 5 (1):33-43, 2006.
I. G. Ovsyannikova, R. M. Jacobson, and G. A. Poland. Variation in vaccine response in normal populations. Pharmacogenomics 5 (4):417-427, 2004.
Subscribe to:
Posts (Atom)