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PubMed1979

Histopathology of nasopharyngeal carcinoma: correlations with epidemiology, survival rates and other biological characteristics.

A total of 363 cases of nasopharyngeal carcinoma (NPC) in Singapore were classified into squamous cell carcinoma (SCC; 73 cases), non-keratinizing carcinoma (NKC; 178 cases) and undifferentiated carcinoma (UC; 172 cases). Possible biological differences between these histologic types and between tumors with and without lymphocytic infiltration were investigated by correlations with survival rates and with selected epidemiologic, immunovirologic, and immunogenetic data on the disease. The 5-year survival rates following radiotherapy were 25.3% for all cases and 58.8% for tumors restricted to the nasopharynx. The 5-year survival rate for SCC was poorer than for the combined NKC and UC groups (p less than 0.05). The 3-year survival rate was better for tumors with lymphocytic infiltration (p less than 0.05), but there were no differences in the 5-year survivals. The survival rates were better in females (p less than 0.01) and in the younger age groups (p less than 0.01). There were no significant correlations between histopathology of NPC and the distributions of cases by age, sex, HLA antigen profiles, or cell-mediated immune status. Squamous cell carcinoma was associated with lower levels of antibodies to the Epstein-Barr nuclear antigen (p less than 0.05), but there were no differences with respect to antibodies against other EBV related antigens. These findings support the view that SCC, NKC, and UC of the nasopharynx, as defined in the WHO classification, are variants of a fairly homogeneous group of neoplasms in the Singapore population.

Adolescent↗
PubMedDate not supplied

Clinical studies of antibodies binding polyriboadenylic acid in systemic lupus erythematosus.

Antibodies of polyriboadenylic acid (poly rA) are demonstrated by filter radioimmunoassay in 75% of patients with systemic lupus erythematosus (SLE), in 54% of patients with discoid lupus erythematosus, and in only 0-7% of normal controls and patients with rheumatoid arthritis or Sjögren's syndrome. These antibodies are distinct from antibodies to single- and double-stranded DNA and double-stranded RNA. Poly rA binding is associated with IgM and IgG serum fractions. Because poly rA may have a role in the transcription of mRNA in mammalian cells and viruses, antibodies to poly rA may be important clues to virologic and immunogenetic mechanisms in the pathogenesis of SLE.

Antibodies↗
PubMed1997

Autoantibodies to a nucleolar RNA helicase protein in patients with connective tissue diseases.

OBJECTIVE: An autoantibody to a nucleolar RNA helicase protein (Gu) was recently discovered in a patient with gastric antral vascular ectasia or watermelon stomach, a disorder that is increasingly being described in systemic sclerosis (SSc). The present study was undertaken to determine whether anti-Gu antibodies occur in connective tissue diseases (CTD) and, if so, to determine their frequencies and any clinical or immunogenetic associations. METHODS: Anti-Gu antibodies were determined by Western blotting of glutathione-purified glutathione S transferase-Gu fusion proteins against consecutive antinucleolar antibody-positive sera (HEp-2 cell substrate) collected over a 5-year period in a rheumatology antinuclear antibody (ANA) testing laboratory. RESULTS: Anti-Gu antibodies were found in 11 (10%) of 108 antinucleolar antibody-positive sera. The subjects with anti-Gu antibodies included 3 of 46 patients with SSc (7%), 3 of 17 patients with systemic lupus erythematosus (18%), 4 of 9 patients with undifferentiated CTD (44%), and 1 healthy relative of an SSc patient. None of the anti-Gu-positive patients had any symptoms suggestive of watermelon stomach. Increased frequencies of both HLA-DQA1*0501 and DQB1*0301 were found, but only DQB1*0301 maintained statistical significance after correction. CONCLUSION: Anti-Gu (nucleolar RNA helicase) antibodies occur in low frequencies in patients with CTDs who have antinucleolar antibodies by ANA testing, but they are not specific for SSc or the watermelon stomach lesion.

Adult↗
PubMed1998

Systemic lupus erythematosus in three ethnic groups: I. The effects of HLA class II, C4, and CR1 alleles, socioeconomic factors, and ethnicity at disease onset. LUMINA Study Group. Lupus in minority populations, nature versus nurture.

OBJECTIVE: To study the relative impact of immunogenetic versus socioeconomic factors on systemic lupus erythematosus (SLE) at disease onset/presentation. METHODS: Medical records regarding SLE onset/ presentation were abstracted on 229 SLE patients who were enrolled in a prospective lupus outcome study. Patients were grouped in equivalent proportions of Caucasians, African Americans, and Hispanics. HLA-DRB1, DQA1, and DQB1 oligotyping, as well as C4 and CR1 allotyping, were carried out by standard methods. In addition to these genetic factors, data on ethnicity, age at SLE onset, monthly income, level of education, and home ownership were entered into stepwise logistic or stepwise multiple linear regression models as independent variables, and each specific clinical feature (neurologic, renal, and cardiovascular disease due to SLE), as well as the total Systemic Lupus Activity Measure (SLAM) score and physician's global assessment of disease activity at disease onset, were entered as dependent variables. RESULTS: HLA-DRB1*0301 (DR3), DRB1*1503 (DR2), and DRB1*08 (DR8) alleles were more frequently found in Caucasians, African Americans, and Hispanics, respectively. Hispanics were more likely to have cardiac and renal disease, as well as a higher physician's global assessment of disease activity. African Americans were more likely to have neurologic disease, renal disease, and a higher SLAM score. Those with less education had a higher SLAM score. Patients with HLA-DRB1*01 had less renal disease and a lower SLAM score. Those with C4A*3 alleles had a higher SLAM score and a higher physician's global assessment of disease activity. CONCLUSION: Both genetic and socioeconomic determinants, as well as other factors associated with Hispanic and African-American ethnicity, affect the presentation of SLE.

Adolescent↗
PubMed1998

Different distribution of HLA class II and tumor necrosis factor alleles (TNF-308.2, TNFa2 microsatellite) in anti-topoisomerase I responders among scleroderma patients with and without exposure to quartz/metal dust.

OBJECTIVE: To investigate the influence of quartz/ metal dust exposure on the pathogenesis of systemic sclerosis (SSc; scleroderma), by an immunogenetic comparison of HLA class II and tumor necrosis factor (TNF) alleles in patients with and without exposure. METHODS: A retrospective study of 30 SSc patients exposed to quartz/metal dust (qSSc) and 50 patients with idiopathic SSc (iSSc) was conducted by DNA-based typing of HLA, TNF-308, and TNFa/b microsatellite alleles. RESULTS: A neutral or protective haplotype in iSSc anti-topoisomerase I (anti-topo I) responders was found to be a susceptibility haplotype in qSSc patients. HLA-DRB1*0301 (DR3), a component of the extended haplotype HLA-DQA1*0501;B1*0201;DRB1*0301; TNF-308.2;TNFa2/b3, had a decreased frequency in iSSc anti-topo I responders compared with non-responders (P = 0.03, odds ratio [OR] 0.11, 95% confidence interval [95% CI] 0.00-0.95), but a significantly increased frequency in qSSc anti-topo I responders compared with controls and with iSSc anti-topo I responders (P = 0.00004, Pcorr = 0.006, OR 11.38, 95% CI 3.17-44.35 and P = 0.0002, Pcorr = 0.02, OR 30.0, 95% CI 2.05-986, respectively). In contrast, DRB1*1104 (DR5) and DRB1*11/15 (DR5/DR2) with no TNF-308.2 and TNFa2 alleles were prevalent in only the iSSc anti-topo I responders compared with controls (P = 0.0005, Pcorr = 0.04, OR 11.0; 95% CI 2.68-45.93 and P = 0.0002, Pcorr = 0.02, OR 12.43, 95% CI 3.65-40.04, respectively). CONCLUSION: The mechanisms that lead to the development of anti-topo I in qSSc and iSSc patients are suggested to be distinct, although it is not clear that the two diseases themselves are different.

Autoantibodies↗
PubMed1999

Genetic risk and protective factors for idiopathic inflammatory myopathy in Koreans and American whites: a tale of two loci.

OBJECTIVE: To better understand genetic contributions to autoimmunity, immunogenetic markers were studied in two racially discrete and geographically isolated populations of patients with idiopathic inflammatory myopathy (IIM). METHODS: Clinical characteristics, as well as clinical and autoantibody subsets, were defined in 151 American white patients and 50 Korean patients with IIM. HLA-DRB1 and DQA1 genotyping was performed on patients and racially matched controls by standard molecular techniques. Gm allotypes and phenotypes were determined by the hemagglutination-inhibition method. RESULTS: HLA-DRB1*0301, the linked allele DQA1*0501, and DRB1 alleles sharing the first hypervariable region motif 9EYSTS13 were major genetic risk factors for the development of myositis in whites (corrected P [Pcorr] < 0.0004, odds ratio [OR] 11.2, 4.5, and 3.1, respectively, for each factor versus controls). Although both the white and Korean patients had a similar distribution of clinical characteristics, autoantibody profiles, and clinical groups, no HLA-DRB1 nor DQA1 allele or motif was found to be a risk factor for IIM in the Korean patients. However, DRB1*14 was a protective factor in Korean patients without myositis-specific autoantibodies (Pcorr = 0.004, OR 0.046). In addition, although no Gm phenotype or allotype was identified as a risk factor in whites, Gm 21 was a protective factor for the development of IIM in Koreans (Pcorr = 0.024, OR 0.3). CONCLUSION: Although myositis patients in the US and Korea share similar clinical and serologic features, the immune response genes predisposing to and protecting from myositis in each of these ethnic groups differ at two chromosomal loci. These data suggest that multiple genetic loci should be studied to identify risk and protective factors for some autoimmune diseases in various ethnic populations.

Adult↗
PubMed1999

No support for HLA-DQ encoded susceptibility in rheumatoid arthritis.

OBJECTIVE: To test predictions based on data from immunogenetic and peptide-binding studies of collagen-induced arthritis in mice, in which it has been suggested that susceptibility to rheumatoid arthritis (RA) might be determined by the interaction between susceptibility alleles at the HLA-DQ locus and protective alleles at the HLA-DRB1 locus (including susceptibility effects for HLA-DQ7 and DQ8). METHODS: Predictions based on these models were tested in 166 healthy controls and 167 patients with RA, all of whom were typed for HLA-DRB1 and HLA-DQ alleles. RESULTS: In this population, HLA-DQ7 did not encode an increased risk for RA. This lack of susceptibility effect of HLA-DQ7 could not be attributed to competing HLA-DQ susceptibility alleles, protective HLA-DRB1 alleles, or the absence of DQA1*0301. CONCLUSION: These observations do not support the DR/DQ hypothesis in its present form.

Alleles↗
PubMed2001

Systemic lupus erythematosus in three ethnic groups. VII [correction of VIII]. Predictors of early mortality in the LUMINA cohort. LUMINA Study Group.

OBJECTIVE: To determine the features associated with mortality in a multiethnic US cohort of patients with systemic lupus erythematosus (SLE) within 5 years of study onset. METHODS: Socioeconomic and demographic features (age, gender, ethnicity, marital status, education, occupation, poverty, and health-related behaviors [drinking, smoking, exercising]), clinical and immunologic features (disease duration, disease onset type, disease activity according to the Systemic Lupus Activity Measure [SLAM], disease damage according to the Systemic Lupus International Collaborating Clinics [SLICC] Damage Index [SDI], number of American College of Rheumatology criteria at diagnosis, organ system manifestations, fatigue and pain ratings, and medication usage and autoantibodies), immunogenetic features (HLA class II genotypes), and behavioral and psychosocial features (social support, illness-related behaviors, and helplessness), as obtained at enrollment into the study, were compared between survivors and deceased patients. Logistic regression analysis was used to determine significant independent risk factors for mortality. RESULTS: Within 5 years of study onset, 34 of 288 patients have died. Fourteen deaths could be directly attributed to SLE and 11 to infections. In 1 patient the cause of death could not be determined. In the remaining 8 patients the cause of death was neither infectious nor disease-related. There were 10 deaths among Hispanics, 18 among African Americans, and 6 among Caucasians (P < 0.05). Variables associated with mortality in the univariable analyses included poverty, less than full-time employment, difficulty in accessing health care, shorter disease duration, cardiovascular and renal involvement, higher serum creatinine levels and lower hematocrit values, higher SLAM and SDI scores, lower use of antimalarial drugs, and higher use of (some) immunosuppressants. Specific autoantibodies and class II HLA genotypes were not associated with mortality. Poverty and higher baseline SLAM and SDI scores were independently associated with mortality in the multivariable analyses. CONCLUSIONS: Disease activity, disease damage, and poverty appear to be the most important determinants of mortality in this multiethnic US cohort of SLE patients. These results have applicability to the management of patients with SLE, a disease that more severely affects disadvantaged minority population groups.

Black or African American↗
PubMed2001

Systemic lupus erythematosus in three ethnic groups. IX. Differences in damage accrual.

OBJECTIVE: To determine the factors predictive of damage in a multiethnic (Hispanic, African American, and Caucasian) LUMINA (lupus in minority populations, nature versus nurture) cohort of patients with systemic lupus erythematosus (SLE) with disease duration of < or =5 years at enrollment (T0). METHODS: Variables (socioeconomic/demographic, clinical, immunologic, immunogenetic, behavioral, and psychological) were measured at T0 and annually thereafter. Disease damage was measured with the Systemic Lupus International Collaborating Clinics Damage Index (SDI), and disease activity was measured with the Systemic Lupus Activity Measure. The relationship between the different variables and the SDI at the last visit (TL) was examined (mean followup from diagnosis to TL 61 months; adjusted for disease duration). Poisson regression was used to identify the independent association between the different variables and SDI scores at TL. RESULTS: Seventy-two Hispanics, 104 African Americans, and 82 Caucasians were included. One-half of patients had not accrued any damage. Caucasians had the lowest SDI scores at T0, and Hispanics had the highest scores at TL. Renal damage occurred more frequently among Hispanics and African Americans, while integument damage was more frequent among African Americans. Neuropsychiatric (20%), renal (16%), and ocular (15%) damage occurred most frequently among all patients. Independent predictors of SDI at TL were age, corticosteroid use (maximum dose at T0), number of American College of Rheumatology (ACR) criteria met, disease activity, and abnormal illness-related behaviors. Other variables were less consistently associated with damage accrual (poverty in African Americans, lack of HLA-DRB1*0301 in Hispanics, presence of HLA-DQB1*0201 and acute onset of SLE in Caucasians). CONCLUSION: Damage in SLE occurs from the outset in some, but not all, patients; Hispanics accrue damage more rapidly. Disease factors (corticosteroid use, number of ACR criteria met, disease activity, and acute-onset type) are important, but age and abnormal illness-related behaviors also contribute to overall damage in SLE.

Adult↗
PubMed1978

Maternal immunological recognition mechanisms during pregnancy.

One of the most intriguing shortcomings of modern immunology, especially transplantation immunology, is its failure to provide a satisfactory final explanation for the consistent non-rejection of immunogenetically alien conceptuses in utero, even in specifically preimmunized females. Certainly, there is no shortage of hypotheses. Over the past few years various observations have utterly refuted the simplistic notion that the much-mated but nulliparous or gravid females are immunologically unaware of the presence and activities of allogeneic cells transiently or chronically within their reproductive tracts. This evidence has engendered the belief that some kind(s) of active response(s) on the part of the female, following early recognitive events, plays an important, if not essential, role, in conjunction with adaptive hypoantigenicity of the trophoblast, not only in conferring selective benefits upon the conceptus from the time of implantation, but also in affording it protection from the possible hazards of a cellular immunity. Evidence is emerging that during mating, implantation, placentation, and gestation (1) various fetal and histocompabibility antigens are presented to the mother in a unique manner; (2) she does respond to these; and (3) her responses aid in the establishment and maintenance of a harmonious state of immunological coexistence with her fetus. There are reasonable grounds for believing that a complete understanding of the immunobiology of the maternal-fetal relationship may facilitate significant advances in both transplantation and tumour immunology.

Animals↗
PubMed1994

HLA-DR53 protects against thrombotic thrombocytopenic purpura/adult hemolytic uremic syndrome.

Class I and Class II HLA antigens were tested in patients treated for thrombotic thrombocytopenic purpura or hemolytic uremic syndrome (TTP/HUS) to determine whether there is a disease association. Based on the results of a pilot trial, retrospective HLA-typing of 18 patients with a diagnosis of TTP/HUS and prospective typing of 12 newly diagnosed patients with TTP/HUS were performed. Twenty-one patients were non-Hispanic Caucasians, 7 were African-Americans, and 2 were Hispanic-Caucasians. Of 30 patients tested, 28 were positive for DR52 (chi-squared = 5.14, P < 0.05), and only two were positive for DR53 compared to 57% of controls (chi-squared = 18.5, P < 0.0005). Diverse DR52 subtypes (DRB3*0101, DRB3*02, and DRB3*0301) were found by oligonucleotide testing in 15 patients, suggesting the association was not with DR52 but with absence of the DR53 antigen. The 2 patients with DR53 were not homozygous. This study suggests that the supertypic antigen, DR53, may govern susceptibility to TTP/HUS, since the relative risk of this disease among DR53 positives is reduced at 0.09 (95% confidence interval, 0.01-0.28). This finding indicates a possible immunogenetic component in the pathogenesis of TTP.

Adult↗
PubMed2004

The association between HLA-DPB1Glu69 and chronic beryllium disease and beryllium sensitization.

BACKGROUND: Several case-control studies have found an association between chronic beryllium disease (CBD) and HLA-DPB1 gene variants. However, the relationship between HLA-DPB1 and beryllium sensitization, and whether the presence of one or two HLA-DPB1(Glu69) alleles is differentially associated with CBD and beryllium sensitization have not been completely resolved. METHODS: Restriction fragment length polymorphism (RFLP) analysis was used to address these questions in a large population-based cohort consisting of 884 beryllium workers (90 with CBD, 64 beryllium sensitized). RESULTS: HLA-DPB1(Glu69) was associated with both CBD (OR = 9.4; 95% CI = 5.4, 16.6) and sensitization (OR = 3.3, 95% CI = 1.9, 5.9). Further, workers with CBD and sensitization were more likely to be homozygous HLA-DPB1(Glu69) compared to workers without disease or sensitization (P < 0.001). CONCLUSIONS: Follow-up of this cohort, scrutiny of HLA-DPB1 haplotypes, and evaluation of gene-environment and gene-gene interactions will be important for fully understanding the immunogenetic nature of this occupational disease.

Alleles↗
PubMed1989

Inherited diseases in North American Mennonites: focus on Old Colony (Chortitza) Mennonites.

The patterns of migration and the genetic disorders occurring among North American Mennonites are reviewed, and inherited conditions recently recognized in a religious and genetic isolate, the Old Colony (Chortitza) Mennonites, are described. Old Colony Mennonites are of Dutch/German origin and descend from approximately 400 founding families who settled in the Old Colony, Chortitza (the Ukraine, USSR) in the late 1700s, and then migrated to Canada and Central and South America in the past century. We investigated over 6 generations of a Canadian Old Colony kindred in which there was extensive intermarriage, and in whom 28 individuals developed diabetes mellitus. Insulin-dependent diabetes mellitus (IDDM) occurred in 14 affected individuals in 10 closely related sibships; the 11 living IDDM patients were all concordant for the immunogenetic marker HLA-DR4. Fourteen close relatives had other disorders of carbohydrate metabolism, including gestational diabetes and non-insulin-dependent diabetes mellitus. Other close relatives had autoimmune diseases, including rheumatoid arthritis, hyper- and hypothyroidism, multiple sclerosis, and red cell aplasia. Other inherited diseases, including Alport syndrome, congenital defects, and inborn errors of metabolism were also found in the kindred. In the almost exclusively (99%) Old Colony Mennonite public health district in which the kindred was ascertained, there were multiple cases of Tourette syndrome, of malformations (including congenital heart defects and cleft lip +/- palate), and familial clusters of inborn errors of metabolism. We report this Old Colony (Chortitza) Mennonite isolate because 1) there are large familial aggregations of tissue-specific autoimmune diseases, malformations, inborn errors of metabolism, and of some other conditions whose genetic basis is still unknown; 2) there are multiple cases of rare genetic conditions, 3) we have established a computerized genealogic data base on over 1,000 kindred members as well as a cryopreserved lymphocyte/DNA bank on over 100 closely related individuals with various genetic conditions; and 4) this religious isolate, which extends across North, Central, and South America, offers an excellent opportunity for studying the epidemiology and molecular genetics of both common and rare inherited diseases.

Adrenal Hyperplasia, Congenital↗
PubMed1993

Schizophrenia: genetics and the maternal immune response to viral infection.

Thirty years ago, Eliot Slater suggested that the reason schizophrenia was not progressively eliminated from the population was that the responsible gene also conveyed a compensatory advantage in terms of increased resistance to infection. If this selective advantage lies in the antibody response to certain viral infections, this could explain recent studies suggesting that exposure to influenza in the second trimester of gestation increases the risk of later schizophrenia. We propose that prenatal exposure to influenza induces maternal antibodies which then cross-react with proteins in the developing foetal brain, becoming foetal autoantibodies. Thus an immunogenetic response by the mother results in aberrant foetal neurodevelopment, the biological substrate for a proportion of adult schizophrenia. Initial research strategies to test this hypothesis are proposed.

Antibodies, Viral↗
PubMed1987

Heterogeneity in myasthenia gravis: HLA phenotypes and autoantibody responses in ocular and generalized types.

HLA phenotypes and autoantibody responses were studied in 71 Japanese patients with myasthenia gravis. HLA-A2, Bw61, and DRw9 were associated with ocular myasthenia gravis (corrected p [CP] less than 0.05 relative risk [RR] = 2.88; CP less than 0.02, RR = 3.60; and CP less than 0.001, RR = 4.63, respectively) and HLA-DRw8 was associated with generalized myasthenia gravis (CP less than 0.001, RR = 5.40). Neither HLA-B8 nor DR3 was found in Japanese patients. The titer of antiacetylcholine receptor antibody (AChR Ab) and the incidence of autoantibodies other than AChR Ab were higher in patients with generalized myasthenia gravis than in those with the ocular type (2.77 +/- 0.62 versus 0.17 +/- 0.03 pmol/ml, p less than 0.001; and 60.6 versus 29.0%, p less than 0.02, respectively). Patients with a high titer of AChR Ab or with autoantibodies had an increased frequency of HLA-DRw8 (CP less than 0.02, RR = 4.61, and CP less than 0.005, RR = 4.53, respectively); whereas patients with a low titer of AChR Ab or without autoantibodies had an increased frequency of HLA-DRw9 (CP less than 0.001, RR = 8.26, and CP less than 0.005, RR = 4.08, respectively). These findings suggest that ocular and generalized myasthenia gravis might have different immunogenetic backgrounds.

Adolescent↗
PubMed1988

HLA haplotype-linked high immune responsiveness against HTLV-I in HTLV-I-associated myelopathy: comparison with adult T-cell leukemia/lymphoma.

HLA haplotypes of 27 patients with human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) and 12 patients with adult T-cell leukemia/lymphoma (ATLL) were examined by analyzing HLA types of the patients and their family members. Either A11Bw54Cw1DR4DQw3, A24Bw54Cw1DR4DQ-, A24B7Cw7DR1DQw1, or A24Bw52Cw-DR2DQw1 and the related haplotypes were found in 70% of cases with HAM. None of these "HAM-associated" haplotypes was found in patients with ATLL. HLA haplotypes made up of HLA components of A26Bw62Cw3DR5DQw3 and one particular haplotype of Aw33B44Cw-DRw6DQw1 were associated with the ATLL haplotypes. These "ATLL-associated" haplotypes were also found in the patients with HAM who had no previous history of blood transfusion. The in vitro cultures of peripheral blood lymphocytes with HTLV-I virion antigens revealed that the response with HAM peripheral blood lymphocytes was remarkably higher than that with ATLL peripheral blood lymphocytes. Based on this HTLV-I-specific immune responsiveness, we can segregate the high responders in HAM (14 of 16 cases) and the low responders in ATLL (6 of 7 cases). The existence of high and low responders was also confirmed by the normal healthy individuals, whose responses were segregated with HAM-associated and ATLL-associated haplotypes. These results suggested that two ethnic groups in southern Kyushu may get the two different diseases, HAM and ATLL, because of their different immunogenetic backgrounds. The high immune response to HTLV-I seems to be an important genetic factor in the development of HAM.

Adult↗
PubMed1994

Natural history of multiple sclerosis.

Multiple sclerosis (MS) is the most common idiopathic inflammatory disease of the central nervous system. The distinction between MS and other benign or fulminant inflammatory demyelinating disorders is based on quantitative, rather than qualitative, differences in chronicity and severity. Primary progressive MS may differ from relapsing-remitting MS in MRI lesion frequency, immunogenetic profile, responsiveness to immunosuppressive treatment, and histology. In 60% of patients, MS begins as a relapsing-remitting disease and evolves secondarily into a progressive neurological illness. Life expectancy is not substantially altered in patients with MS, particularly in the early years of the illness. The rate of suicide has been reported to be increased sevenfold in MS patients. Up to 40% of patients with attacks severe enough to render them nonambulatory may not recover. At 15 years from MS onset, 50% of patients are disabled to the point at which they at least require a cane to walk a half block. Early age at onset, female sex, relapsing-remitting course at onset, and perhaps optic neuritis or sensory symptoms at onset and relatively few attacks in the first two years are associated with a favorable course.

Adult↗
PubMed1997

Genetic predisposition to multiple sclerosis as revealed by immunoprinting.

This study was designed to examine the immunogenetic background predisposing to multiple sclerosis (MS). Three hundred fifty-eight clinically well-characterized MS patients from Germany were investigated and compared to 395 healthy control subjects. Each individual was genotyped for 22 polymorphic markers located within or close to immunorelevant candidate genes including HLA-DRB1*, T-cell receptor (TCR), cell interaction molecules, cytokines, and cytokine receptor genes. Altogether, approximately 17,000 genetic analyses were performed. Patients were grouped according to the course of MS-relapsing-remitting or chronic progressive. Most of the genetic markers were not associated with increased risk or their exact contribution was not clear (e.g., tumor necrosis factor). The relative risks for HLA-DRB1*15+ and DRB1*03+ individuals were 3.64 and 1.42, respectively. In both groups of patients, certain TCRB gene polymorphisms were risk factors. In DRB1*03+ individuals the relative risk was increased (> 22) when a specific TCRBV6S3 allele was also inherited. Furthermore, distinct linkage disequilibria of TCRBV6S1/TCRBV6S3 elements in patients and control subjects strongly suggested an additional risk factor in the TCRBV region for DRB1*15+ individuals. These findings are discussed with respect to the pathogenesis and rational approaches to the therapy of MS.

Adolescent↗