Biomedical subjects

J D Reveille

Publications and source records attributed to J D Reveille.

At least 55 records · Page 3Linked to original sources

PubMed2000

Autoantibodies to fibrillin 1 in systemic sclerosis: ethnic differences in antigen recognition and lack of correlation with specific clinical features or HLA alleles.

OBJECTIVE: We previously reported the presence of autoantibodies to the extracellular matrix protein, fibrillin 1, in sera from patients with systemic sclerosis (SSc). These autoantibodies appeared to be highly disease-specific but had significantly different frequencies among ethnic groups. The aims of this study were 3-fold: 1) to determine whether sera from SSc patients of different ethnic backgrounds recognized different antigenic epitopes of fibrillin 1, 2) to determine whether sera from patients with polymyositis/dermatomyositis (PM/DM) with or without interstitial lung disease (ILD) also produced these antibodies, and 3) to determine any correlation of anti-fibrillin 1 antibodies with specific clinical features of SSc, other autoantibodies, or HLA class II alleles in a prospectively studied cohort of SSc patients with early (<5 years' duration) disease (the Genetics versus Environment In Scleroderma Outcome Study [GENISOS] cohort). METHODS: Three recombinant peptides accounting for the N-terminal end, proline-rich C region, and epidermal growth factor-like calcium-binding (EGF-cb) domains of fibrillin 1 were used in a radioimmunoassay to screen sera from a large group of SSc and PM/DM patients and ethnically matched controls. RESULTS: The majority of Choctaw American Indians, Japanese, and African Americans with SSc produced IgM and/or IgG autoantibodies to one or more recombinant fibrillin 1 proteins, while <50% of Caucasians with SSc showed seroreactivity. There were striking ethnic differences in fibrillin 1 antigenic epitope recognition among these ethnic groups. African American SSc sera recognized primarily the N-terminal end, and Caucasian sera mostly recognized the EGF-cb repeats and the proline-rich C region. In contrast, most Choctaw American Indian and Japanese SSc sera appeared to recognize 2 or 3 epitopes, respectively. PM/DM patient sera did not recognize any of the fibrillin 1 epitopes regardless of the presence of ILD. In the prospective, multiethnic GENISOS cohort, the presence of anti-fibrillin 1 antibodies did not correlate with any major clinical manifestations, other autoantibodies, or HLA class II alleles. CONCLUSION: There are striking ethnic differences in antigenic epitope specificity of anti-fibrillin 1 antibodies in patients with SSc, and the majority of SSc patients, except for Caucasians, produce antibodies to fibrillin 1. The antifibrillin response thus far remains specific for scleroderma syndromes, but it does not correlate with any major clinical features, other autoantibodies, or HLA class II alleles.

Alleles↗

PubMed2000

The changing spectrum of rheumatic disease in human immunodeficiency virus infection.

CONTEXT: Although it has been known for over 15 years that a number of rheumatic diseases occur in patients with human immunodeficiency virus (HIV) infection, increasing knowledge about these disorders and advances in HIV treatment need to be considered in approaching patients with HIV-associated rheumatic disease. OBJECTIVE: To examine the clinical, pathologic, and therapeutic features of HIV-associated rheumatic diseases in the context of what is known about the immunology of HIV infection. DATA SOURCES: The author's own extensive collection of references, supplemented by PubMed Medline searches for articles in English-language journals published between 1985 and 2000. The indexing term HIV and the following coindexing terms were used for searching: arthritis, Reiter's syndrome, psoriatic arthritis, rheumatoid arthritis, osteonecrosis, vasculitis, pulmonary hypertension, myositis, myopathy, fibromyalgia, septic arthritis, parotid enlargement, diffuse infiltrative lymphocytosis syndrome, systemic lupus erythematosus, septic arthritis, mycobacterial arthritis, fungal arthritis, autoantibodies, anti-cardiolipin antibodies, and anti-neutrophilic cytoplasmic antibodies. STUDY SELECTION: All papers identified in the literature search were reviewed. Studies presenting data that merely confirmed previous studies were not included in the analysis. DATA EXTRACTION: All identified papers were abstracted by the author. Letters to the editor were included only if a new observation had been made. DATA SYNTHESIS: This was a qualitative review of papers published, with new knowledge about these disorders summarized and presented. RESULTS: Despite new treatments for HIV, reports of rheumatic diseases presenting in AIDS patients persist, especially in HIV-associated arthritis, diffuse infiltrative lymphocytosis syndrome, HIV-associated vasculitis, and polymyositis. However, new HIV treatments may ameliorate these diseases. CONCLUSIONS: The spectrum of HIV-associated rheumatic disease remains a diagnostic and therapeutic challenge for the clinician. The impact of changes in HIV treatment on these disorders requires further assessment.

Anti-HIV Agents↗

PubMed2000

Systemic lupus erythematosus in three ethnic groups. VI: Factors associated with fatigue within 5 years of criteria diagnosis. LUMINA Study Group. LUpus in MInority populations: NAture vs Nurture.

OBJECTIVE: To determine the frequency, degree and associated features of fatigue among Hispanic (H), African American (AA) and Caucasian (C) patients with recent onset (< or = 5 yr) systemic lupus erythematosus (SLE) at their baseline evaluation. METHODS: H (n = 69), AA (n = 83) and C (n = 71) patients from the LUMINA (LUpus in MInority populations: NAture vs Nurture) cohort were studied. Fatigue [Fatigue Severity Scale (FSS)] was defined as present if FSS score > or = 3.0. Variables from functional, clinical, sociodemographic, health behaviors, behavioral and psychological and immunogenetics domains were ascertained at study entry. Associations were examined using regression models. RESULTS: Eighty-six percent (85.7%) of patients reported having fatigue (82.6% H; 85.5% AA; 88.7% C); median FSS score, 5.3. Factors from the psychological and clinical domains were primarily associated with FSS; immunogenetic (HLA Class II phenotypes) features were not. Increased fatigue was strongly associated with decreasing function, both physical and mental. Variables associated with significantly greater degree of fatigue at baseline in the multivariable stepwise model in order of decreasing additional partial R2 explained included: abnormal illness-related behaviors, older age, higher self-reported pain, greater degree of helplessness, greater disease activity, Caucasian race, and lacking health insurance (model R2 = 37%). CONCLUSIONS: Fatigue is one of the most prevalent clinical manifestations of SLE across all ethnic groups. The perception of fatigue severity in SLE may be multifactorial in origin, including psychosocial factors and disease activity. If these prove causal, knowledge of their contribution may suggest therapeutic and/or behavioral interventions, which could ameliorate this pervasive and often incapacitating symptom of SLE.

Black or African American↗

PubMed2000

Frequency of HLA-DQB*06 in Caucasian,African American, and Mexican American patients with a positive direct antiglobulin test.

A reduced frequency of HLA-DQ6 in patients with a positive direct antiglobulin test (DAT) was previously reported but race was undisclosed. Therefore, we investigated a total of 275 patients (80 Caucasian, 113 African American, and 82 Mexican American) and 518 normal controls (205 Caucasian, 208 African American, and 105 Mexican American). These were typed for class II HLA antigens using molecular techniques. A DAT was performed on each patient's red cells drawn into EDTA using both mouse and rabbit polyspecific reagents. Of 275 patients tested, 73 (27%) had a positive DAT (12 Caucasians, 35 African Americans, and 26 Mexican Americans). We found that 5 (42%) Caucasian patients and 103 (50%) Caucasian controls possessed the DQB*06 allele (p =.56). In the African American group, 15 (43%) patients and 91 controls (44%) were DQB*06 positive (p =.92). Six Mexican American patients (23%) and 21 controls (20%) had the DQB*06 allele (p =.72). This article underscores the need to use race-matched controls when genetic disease associations are sought.

Journal Article↗

PubMed1999

Associations of anti-beta2-glycoprotein I autoantibodies with HLA class II alleles in three ethnic groups.

OBJECTIVE: To determine any HLA associations with anti-beta2-glycoprotein I (anti-beta2GPI) antibodies in a large, retrospectively studied, multiethnic group of 262 patients with primary antiphospholipid antibody syndrome (APS), systemic lupus erythematosus (SLE), or another connective tissue disease. METHODS: Anti-beta2GPI antibodies were detected in sera using an enzyme-linked immunosorbent assay. HLA class II alleles (DRB1, DQA1, and DQB1) were determined by DNA oligotyping. RESULTS: The HLA-DQB1*0302 (DQ8) allele, typically carried on HLA-DR4 haplotypes, was associated with anti-beta2GPI when compared with both anti-beta2GPI-negative SLE patients and ethnically matched normal controls, especially in Mexican Americans and, to a lesser extent, in whites. Similarly, when ethnic groups were combined, HLA-DQB1*0302, as well as HLA-DQB1*03 alleles overall (DQB1*0301, *0302, and *0303), were strongly correlated with anti-beta2GPI antibodies. The HLA-DR6 (DR13) haplotype DRB1*1302; DQB1*0604/5 was also significantly increased, primarily in blacks. HLA-DR7 was not significantly increased in any of these 3 ethnic groups, and HLA-DR53 (DRB4*0101) was increased in Mexican Americans only. CONCLUSION: Certain HLA class II haplotypes genetically influence the expression of antibodies to beta2GPI, an important autoimmune response in the APS, but there are variations in HLA associations among different ethnic groups.

Alleles↗

PubMed1999

Systemic lupus erythematosus in three ethnic groups. IV. Factors associated with self-reported functional outcome in a large cohort study. LUMINA Study Group. Lupus in Minority Populations, Nature versus Nurture.

OBJECTIVE: To identify features of systemic lupus erythematosus (SLE) associated with poor functional outcome as measured by the 36-item Medical Outcomes Study Short Form 36 Health Survey (SF-36). METHODS: Two hundred twenty-four patients with early SLE (70 Hispanic, 83 African American, and 71 white) enrolled in a longitudinal study of outcomes were evaluated at study entry. The 8 composite scales and 2 summary measures (physical and mental) of the SF-36 were the dependent variables. Independent variables--1) sociodemographic, 2) clinical features, 3) immunologic, 4) global scores, and 5) behavioral/cultural--were examined for each of the scales and summary measures and for each ethnic group. Significant variables in these analyses were then used to construct models to determine their association with each of the scales and the 2 summary measures for the entire population and the 3 ethnic groups. RESULTS: Self-reported physical and mental functioning were most consistently associated with abnormal illness-related behaviors, helplessness, fatigue, and pain at study entry. Helplessness was more strongly associated with functioning in the Hispanics than in the African American or white patients. Pain was strongly associated with physical but not mental health. The models were quite robust, accounting for 41% to 68% of the variance for the two summary measures. CONCLUSION: Patients' attitudes toward their disease, fatigue, and pain have greater impact on self-perceived functional levels, as measured by the SF-36, than do more objective measures of disease activity and damage such as the presence of specific autoantibodies and/or the occurrence of specific organ involvement. Interventions designed to improve outcome may need to include ethnic-specific as well as general strategies.

Activities of Daily Living↗

PubMed1999

Systemic lupus erythematosus in three ethnic groups. V. Acculturation, health-related attitudes and behaviors, and disease activity in Hispanic patients from the LUMINA cohort. LUMINA Study Group. Lupus in Minority Populations, Nature versus Nurture.

OBJECTIVE: To assess the relationship between acculturation and clinical, socioeconomic-demographic, and behavioral/psychosocial features in Hispanic patients with systemic lupus erythematosus (SLE) from the LUMINA (Lupus in Minority Populations, Nature versus Nurture) cohort. METHODS: An empirically derived questionnaire was administered to 67 Mexican American SLE patients participating in a longitudinal study of outcome. This questionnaire inquired about place of birth, upbringing and length of stay in the United States, language (proficiency, usage, and preferences; English/bilingual versus Spanish), type of neighborhood, self-identity, and social interactions. Responses to this questionnaire and an informal interaction with a single bilingual, bicultural Mexican American research assistant were used to generate a score on a 10-cm anchored visual analog scale (VAS) (0 = no acculturation and 10 = maximum acculturation). The responses to the questionnaire were then quantified and scored by a physician who was unaware of the VAS. A composite score was then obtained utilizing 4 of the 6 components of the instrument. The VAS was found to have adequate sensitivity (91%), specificity (88%), and overall predictive value (89%) when the composite score was used as the validity criterion. Therefore, the VAS was used in all subsequent analyses; the median in this VAS separated patients into high and low acculturation groups. The relationship between acculturation and sociodemographic, behavioral/psychosocial (social support, abnormal illness-related behaviors, and helplessness) and clinical variables (disease duration, onset type, number of American College of Rheumatology criteria met, disease activity, and damage) at study entry was then explored. RESULTS: Patients in the low acculturation group had fewer years of education, were less likely to have private health insurance, and had less social support as compared with those in the high acculturation group; they also exhibited less disease activity as determined by the overall physician and patient global assessments of the Systemic Lupus Activity Measure. Abnormal illness-related behaviors and helplessness were not increased in the low acculturation group. CONCLUSIONS: Low levels of acculturation were associated with indicators of low socioeconomic status, but also with less disease activity at enrollment into LUMINA; they were, however, not associated with more abnormal illness-related behaviors or with helplessness, as measured in this study. The possible impact of acculturation and of its mediators in the course and outcome of SLE among Hispanic patients needs to be determined longitudinally.

Acculturation↗

PubMed1999

HLA associations of anti-beta2 glycoprotein I response in a Greek cohort with antiphospholipid syndrome and meta-analysis of four ethnic groups.

Using molecular typing, we evaluated the strength of class II HLA associations in 67 Greek patients with antiphospholipid syndrome (APS), 54 of whom had antibodies against beta2-glycoprotein I (beta2GPI), as compared to 246 controls. To further clarify and delineate HLA associations of the beta2GPI response, we combined these data with individual patient data from three other ethnic groups including an additional 74 patients with beta2GPI response and 403 ethnically matched controls of white, African-American, and Mexican-American origin in a formal meta-analysis. The major alleles associated with anti-beta2GPI response are HLA-DQA1*03 (in particular *0301) and the HLA-DRB1*1302-DQB1*0604 haplotype, while protection against developing an anti-beta2GPI response is related primarily to the HLA-DRB1*0101-DQA1*0101 haplotype and the HLA-DRB1*1101 allele. These effects are not significantly heterogeneous across ethnic groups. The previously observed association with HLA-DQB1*0302 may simply reflect linkage disequilibrium with HLA-DQA1*0301 and the previously reported HLA-DQB1*06 effect is limited to HLA-DQB1*0604/0605, while HLA-DQB1*0602 is unlikely to be important. The meta-analysis clearly documents that the anti-beta2GPI response is determined by a few specific class II alleles and haplotypes.

Antiphospholipid Syndrome↗

PubMed1999

HLA haplotypes and microsatellite polymorphisms in and around the major histocompatibility complex region in a Native American population with a high prevalence of scleroderma (systemic sclerosis).

Choctaw Native Americans in southeastern Oklahoma have the highest prevalence of scleroderma or systemic sclerosis yet found (469/100,000). An Amerindian HLA DR2 haplotype (DRB1*1602) was significantly associated with scleroderma in this population in a previous study. It is not known, however, if other disease genes are linked to this HLA haplotype. The regions flanking the HLA loci were studied with polymorphic microsatellite markers. An extended HLA DR2 (DRB1*1602, DQA1*0501, DQB1*0301, DPB1*1301) haplotype that includes the class I and III regions was identified which was significantly associated with scleroderma in the Oklahoma Choctaw. No other significant associations with microsatellite marker alleles immediately flanking the HLA region were found.

Autoimmune Diseases↗

PubMed1999

Alopecia areata in families: association with the HLA locus.

Alopecia areata (AA) is a T cell mediated disease directed against hair follicles that results in bald patches. It can range in severity from patchy (AA), to total scalp hair loss (alopecia totalis; AT) or body hair loss (alopecia universalis; AU). We have previously shown that HLA-DR4 and DR11 as well as HLA-DQ*03 alleles are increased in unrelated AA patients compared with controls. To study whether class II HLA alleles are linked to AA, we investigated 81 extended families that included 192 AA patients, including 89 with AT or AU. We also performed the transmission disequilibrium test (TDT) in 143 nuclear families. Results showed an association between alleles of HLA-DQB (p = 0.014) and HLA-DR (p = 0.010). We also performed linkage analysis in 75 families whose members' genomic DNA were available for HLA typing. Results from this analysis support linkage between AA and class II loci with a maximal LOD score of 2.42 to HLA-DQB at 5% recombination, and with a maximal LOD score of 2.34 to HLA-DR at 0% recombination. There was an increased incidence of atopic dermatitis and autoimmune thyroiditis in families. AA appears to be a class II HLA restricted organ specific immune response to the hair follicle.

Alleles↗

PubMed1999

Systemic lupus erythematosus in three ethnic groups: III. A comparison of characteristics early in the natural history of the LUMINA cohort. LUpus in MInority populations: NAture vs. Nurture.

AIM: To determine and contrast the socioeconomic-demographic and clinical features of patients with recent onset (< or =5 y) systemic lupus erythematosus (SLE) from three ethnic groups, Hispanic, African-American and Caucasian (H, AA, C). SUBJECTS AND METHODS: SLE cases (American College of Rheumatology criteria) (incident (n = 56), prevalent (n = 173)), were enrolled in a longitudinal study at The University of Alabama at Birmingham, The University of Texas-Houston Health Science Center and The University of Texas Medical Branch at Galveston. Socioeconomic-demographic, clinical, immunological, behavioral and psychological data were obtained using validated instruments and standard laboratory techniques, and compared. RESULTS: 70 H, 88 AA and 71 C SLE patients constitute this cohort. H and AA patients were younger and of lower socioeconomic-demographic status. They also had evidence of more frequent organ system involvement (renal, cardiovascular), more auto-antibodies, more active disease (after adjusting for discrepant socioeconomic-demographic features), lower levels of social support and more abnormal illness-related behaviors (more in H than in AA). H also were more likely to have an abrupt disease onset; C were more likely to be on antimalarials but less likely to be on corticosteroids. H, AA, and C used health care resources comparably. They had similar levels of pain and physical and mental functioning after adjusting for age, disease duration, income, education, social support, illness-related behaviors, and Systemic Lupus Activity Measure or SLAM scores. CONCLUSIONS: H and AA patients have more active SLE, at an earlier age of onset, and a less favorable socioeconomic-demographic structure (worse among the H than AA) which predispose them to a less favorable natural history.

Adolescent↗

PubMed1998

Prevalence of the diffuse infiltrative lymphocytosis syndrome among human immunodeficiency virus type 1-positive outpatients.

OBJECTIVE: To ascertain the prevalence of the diffuse infiltrative lymphocytosis syndrome (DILS) in human immunodeficiency virus type 1 (HIV-1)-positive outpatients. METHODS: The presence of sicca symptoms and visible salivary gland enlargement was determined by interview and physical examination, and the clinical stage was determined by chart review, in 523 HIV-positive patients. The diagnosis of DILS was established in those with parotid gland enlargement by minor salivary gland biopsy or radionuclide scintigraphy. RESULTS: Definite DILS was found in 15 (3%) of the 523 patients, and possible DILS in 18 (3.4%). The prevalence of definite DILS was significantly higher in African Americans (4.5%). Self-reported facial swelling and xerophthalmia that was not explained by the effects of medication were found more frequently in those with DILS than in the non-DILS patients. Patients with DILS had higher CD8 counts (mean +/- SD 1,456 +/- 813/mm3) compared with those without DILS (934 +/- 624/mm3; P < 1 x 10(-6)), and were less advanced in their HIV clinical stage (Centers for Disease Control and Prevention stages A or B in 76% compared with 60% of the non-DILS group; P = 0.01). CONCLUSION: DILS is an important problem in HIV-infected outpatients and tends to occur in patients whose clinical disease is at a less advanced stage. Patients with parotid gland enlargement accompanied by sicca symptoms should be screened for HIV infection.

Diagnosis, Differential↗

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

Systemic lupus erythematosus in three ethnic groups: II. Features predictive of disease activity early in its course. LUMINA Study Group. Lupus in minority populations, nature versus nurture.

OBJECTIVE: To determine the factors associated with disease activity in patients with recent-onset (< or =5 years) systemic lupus erythematosus (SLE) who were of Hispanic, African-American, or Caucasian ethnicity. METHODS: Incident and prevalent cases of SLE, as defined by the American College of Rheumatology criteria for SLE, among the 3 ethnic groups were identified in Alabama (The University of Alabama at Birmingham) and Texas (The University of Texas-Houston Health Science Center and The University of Texas Medical Branch at Galveston). Variables from the sociodemographic, clinical, immunologic, immunogenetic, behavioral, and psychological domains were obtained using validated instruments. Disease activity was ascertained with the Systemic Lupus Activity Measure (SLAM). Stepwise domain regressions with SLAM score as the dependent variable were performed. Final ethnic-specific and overall regression models were obtained by entering variables that were retained in the domain regressions. RESULTS: SLAM scores at study entry were higher in the African Americans (mean +/- SD 12.6 +/- 6.9) and Hispanics (11.0 +/- 6.2) than in the Caucasians (8.5 +/- 3.7) (P < or = 0.001). The final overall regression model (R2 = 28%) for higher SLAM score included the following variables: African-American ethnicity, lack of private health insurance, abrupt disease onset, presence of anti-Ro antibodies, absence of HLA-DRB1*0301, higher levels of helplessness, and abnormal illness-related behaviors. CONCLUSION: Socioeconomic, immunologic, immunogenetic, behavioral, and psychological variables were all predictive of disease activity early in the course of SLE, irrespective of ethnic group. However, there remain ethnic group differences in disease activity that were not explained by these factors.

Adolescent↗

PubMed1998

The immunogenetics of the seronegative spondyloarthropathies.

In none of the rheumatic diseases has the genetic contribution to pathogenesis been so well characterized as in the seronegative spondyloarthropathies. Most important has been the elucidation of the structure and effect on disease expression of HLA-B27, where 11 subtypes have been distinguished to date. These vary in frequency in different ethnic groups and seem to show differential disease associations. The high frequency of this gene in patients with the seronegative spondyloarthropathies, especially ankylosing spondylitis (AS) and Reiter's syndrome (RS)/reactive arthritis (ReA), has emerged as probably the best example of a disease association with a hereditary marker. Other HLA genes, in addition to HLA-B27, have been implicated in psoriasis and psoriatic arthritis. These include those from the HLA-C locus and from HLA-DR. In addition, recent family studies have implicated other genes outside the MHC that further enhance the susceptibility to AS.

Amino Acid Sequence↗

PubMed1998

HLA-B27 and the seronegative spondyloarthropathies.

In the 25 years since the initial reports of the association of HLA-B27 with ankylosing spondylitis (AS) and subsequently with Reiter's syndrome, psoriatic spondylitis, and the spondylitis of inflammatory bowel disease, the association of HLA-B27 with the seronegative spondyloarthropathies has remained one of the best examples of a disease association with a hereditary marker. HLA-B27 has been recognized as representative of a spectrum of diseases, ranging from the majority of HLA-B27-positive individuals who have no disease at all, through those with isolated eye or skin involvement, to those with critical eye, heart, and peripheral joint compromise of full-blown AS. Yet HLA polymorphism has evolved in response to environmental stresses, and even the presence of HLA-B27 itself appears to confer advantages in certain infectious diseases, such as acquired immune deficiency syndrome (AIDS). This article will review what is currently known about HLA-B27 and disease, especially in the seronegative spondyloarthropathies. The structure-function relationship of HLA-B27 will be presented, including differences between the B27 subtypes both in their ethnic variation and possible disease implications. The disease spectrum conferred by the presence of HLA-B27 will also be discussed, and the theories of how HLA-B27 contributes to the pathogenesis of the spondyloarthropathies will be considered.

Amino Acid Sequence↗

PubMed1998

The genetic contribution to the pathogenesis of rheumatoid arthritis.

The association of HLA-DR4 or other HLA-DRB1 alleles excoding the shared (or rheumatoid) epitope has now been established in nearly every population. Similarly, the fact that the presence and gene dosage of HLA-DRB1 alleles affect the course and outcome of rheumatoid arthritis has likewise been seen in most (although not all) studies. Family studies are making it increasingly clear that other genes are involved in the pathogenesis of rheumatoid arthritis, both within and outside of the major histocompatibility complex, and much work is ongoing to help identify them and their impact on the disease. This article reviews where we stand in the knowledge of HLA and other genes and their associations with predisposition to and outcome in rheumatoid arthritis.

Alleles↗

PubMed1998

Autoantibodies to beta2-glycoprotein I in systemic lupus erythematosus and primary antiphospholipid antibody syndrome: clinical correlations in comparison with other antiphospholipid antibody tests.

OBJECTIVE: To examine relationships between anti-beta2-glycoprotein (beta2-GPI) antibodies and other antiphospholipid antibody (aPL) tests (aPL ELISA and the lupus anticoagulant or LAC) and the associations of each of these aPL tests with individual clinical manifestations of the antiphospholipid antibody syndrome (APS). METHODS: IgG and IgM anti-beta2-GPI antibodies were determined by ELISA in 281 patients with SLE, primary APS, or other connective tissue diseases. Frequencies, sensitivities, specificities, and predictive values and correlations of anti-beta2-GPI were compared to the aPL ELISA (IgG and IgM) and LAC for individual (and combined) features of APS. RESULTS: Among 139 patients with positive aPL ELISA and/or LAC tests, 57 (41%) had anti-beta2-GPI antibodies (IgG and/or IgM) compared to 11% of patients with SLE negative for these tests (p = 0.00001). In 130 patients with APS, anti-beta2-GPI occurred in 42% and tended to be more specific but less sensitive than the aPL ELISA or LAC. When all 3 aPL tests were combined, the best sensitivities and negative predictive values were achieved; however, specificity and positive predictive values remained low. Anti-beta2-GPI antibodies occurred more frequently in primary APS (58%) vs secondary antiphospholipid syndromes (33%) (p = 0.008, OR = 2.9). Among 79 patients with SLE negative by both aPL ELISA and LAC, 9 (11 %) were positive for anti-beta2-GPI, 7 of whom had clinical features consistent with APS (representing 5% of all with APS). Stepwise multiple logistic regression analysis revealed beta2-GPI to be most strongly associated with neurological syndromes other than stroke, deep venous thrombosis, and recurrent fetal loss, while LAC was most strongly correlated with stroke and thrombocytopenia. IgM aPL antibodies also were independently associated with neurological syndromes and recurrent fetal loss. CONCLUSION: Testing for beta2-GPI antibodies may be clinically useful in the diagnosis of APS but cannot supplant other aPL ELISA or LAC. Multivariate analyses suggest that anti-beta2-GPI antibodies may play a more central role in certain clinical manifestations of APS than antibodies detected by the aPL ELISA or LAC.

Antibodies, Antiphospholipid↗