Restriction fragment length polymorphism analysis of HLA-DR, DQ, DP and C4 alleles in Caucasians with systemic lupus erythematosus.

HLA-DR, DQ, DP and C4 null alleles were determined by restriction fragment length polymorphism (RFLP) analysis in 60 Caucasian patients with systemic lupus erythematosus (SLE) and 66 controls. DR3 (DRw17) and DQw2.1 were increased in frequency in the patients with SLE associated with the presence of C4A null genes.

HLA-D locus associations in alopecia areata. DRw52a may confer disease resistance.

Because predisposition to autoimmunity has been associated with HLA-D alleles and alopecia areata is hypothesized to be a T-cell mediated autoimmune hair loss, we determined DR and DQ alleles in 88 white and 10 American black patients with alopecia areata as well as controls with the use of restriction fragment length polymorphism typing with cDNA probes. White patients with alopecia areata have an increase in the phenotype frequencies of DR4 and DQw8 and an increase in genotype frequencies of DR4 and DR5 (now DRw11[5]). These associations are in agreement with those reported in two other studies but are not significant when corrected by the number of HLA antigens tested.

Human immunodeficiency virus-associated psoriasis, psoriatic arthritis, and Reiter's syndrome: a disease continuum?

The presence of peripheral arthritis and HLA-A, B, C, DR, and DQ antigens was evaluated prospectively in 18 Caucasian men with human immunodeficiency virus-associated psoriasis. An asymmetric polyarthritis occurred in 32% of the patients and correlated with the presence of HLA-B27. Extensive clinical overlap between psoriatic arthritis, psoriasis, and Reiter's syndrome was noted.

HLA-D region genes associated with autoantibody responses to histidyl-transfer RNA synthetase (Jo-1) and other translation-related factors in myositis.

Myositis has been associated with HLA-B8 and DR3, especially in white patients with polymyositis and serum anti-Jo-1 antibodies. Twenty-eight patients with myositis and serum translation-related autoantibodies anti-Jo-1, anti-PL-7, anti-PL-12, anti-KJ, and anti-SRP were studied for HLA class II specificities by Southern blotting with HLA-DR beta, DQ beta, and DQ alpha probes. The association of HLA-DR3 (DRw17) with anti-Jo-1 antibodies in white myositis patients was confirmed (P = 0.

Prognosis in systemic lupus erythematosus. Negative impact of increasing age at onset, black race, and thrombocytopenia, as well as causes of death.

To assess the impact of demographic and clinical factors on prognosis in patients with systemic lupus erythematosus (SLE), we examined survivorship by life-table analysis in 389 patients. There were approximately equal numbers of Caucasian patients and American black patients in this study group. On both univariate and multivariate analyses, we found that both American black race and increasing age at SLE onset independently worsened the probability of survival.

DNA analysis of HLA-DR and DQ genes in American blacks with systemic lupus erythematosus.

We studied DNA polymorphisms of HLA-DR and DQ alleles in 63 American black patients with systemic lupus erythematosus (SLE). We found no HLA-DR beta, DQ alpha, or DQ beta restriction fragment length polymorphism (RFLP) or RFLP-determined DR or DQ specificity associated with SLE in either the patients or in 57 control subjects. DRw52b was positively associated with renal involvement and negatively associated with anti-nuclear RNP antibodies.

Genetic studies in Sjögren's syndrome and systemic lupus erythematosus.

HLA associations with Sjögren's syndrome (SS), previously defined by serologic HLA typing, are reviewed. Because the SS-A/Ro and SS-B/La autoantibody responses in SS and systemic lupus erythematosus (SLE) show even stronger correlations with HLA alleles, HLA-DR and DQ alleles were examined using restriction fragment length polymorphisms (RFLP) in white and black patients with SS and/or SS having anti-Ro and anti-La antibodies. The strongest associations across ethnic lines were with HLA-DR3, DQw2 and DQw1.

Predicting individual differences in pain and functional impairment among patients with rheumatoid arthritis.

Objective measures of disease activity (erythrocyte sedimentation rate and joint swelling), disease severity (radiographic ratings), and psychological variables (coping strategies and affective states) were used to predict the degree of pain and functional impairment that would be experienced by a group of 53 patients who had rheumatoid arthritis. The severity of disease demonstrated no significant relationship to measures of outcome. Multiple regression analyses revealed that psychological variables explained a substantial proportion of the variance in outcome scores, even after disease activity was taken into account.

Genetic studies of Ro (SS-A) and La (SS-B) autoantibodies in families with systemic lupus erythematosus and primary Sjögren's syndrome.

Using enzyme-linked immunosorbent assays, autoantibodies to Ro (SS-A) were detected in the sera of 21% of the first-degree relatives and 11% of the second-degree relatives of anti-Ro-positive probands with systemic lupus erythematosus (SLE) or primary Sjögren's syndrome, as compared with 3% of normal control subjects (P = 0.003 and P = 0.09, respectively).

Familial polyarteritis nodosa: a serologic and immunogenetic analysis.

Familial polyarteritis nodosa (PAN) is a rarely described entity. We describe a family with 2 members with PAN after a common hepatitis B infection. Many other autoimmune diseases and autoantibodies were found in other family members not corresponding to HLA phenotypes, suggesting other non-HLA-linked genetic influences may be operative in predisposition to PAN.

C4A gene deletion and HLA associations in black Americans with systemic lupus erythematosus.

In North America and European Caucasoids with systemic lupus erythematosus (SLE) there is an increased frequency of a C4A, CYP21A gene deletion, largely associated with the HLA-B8,DR3,C4A*QO extended haplotype. There have been no consistent HLA associations reported for SLE in blacks, although an increased frequency of serologically determined C4A null alleles has been reported in two studies. We studied 79 black American SLE patients and 68 black controls by restriction fragment length polymorphism analysis to determine if a C4A gene deletion was a genetic risk factor for SLE.

Restriction fragment length polymorphism analysis in ankylosing spondylitis.

We utilized the technique of restriction fragment length polymorphism (RFLP) analysis in order to examine class I major histocompatibility complex genes in 52 Alabama ankylosing spondylitis patients and 107 local control subjects. A 9.2-kilobase PvuII RFLP was identified using the class I-specific B7 cDNA probe pDP001 that was closely associated with ankylosing spondylitis, most specifically with peripheral joint (including shoulder and hip) involvement.

Major histocompatibility complex genes in systemic lupus erythematosus, Sjögren's syndrome, and polymyositis.

Current concepts about the roles of human leukocyte antigen (HLA) and complement genes in predisposing to connective tissue diseases are reviewed. Precise localization of disease conferring alleles and epitopes is confounded by two major phenomena: (1) clinical and serologic heterogeneity of the diseases and associations of several different HLA alleles with different and often overlapping autoantibody responses; and (2) linkage disequilibrium of many potentially relevant gene loci located on the disease-associated HLA haplotypes. Using molecular genetic tools in serologically homogeneous patient populations, and across racial lines, the Ro (SS-A) and la (SS-B) autoantibody responses in systemic lupus erythematosus and Sjögren's syndrome appear to associate most strongly with HLA-DQ alleles, whereas the anti-Jo-1 autoantibody in myositis correlates best with HLA-DRw52.

Clinically significant valvular heart disease in systemic lupus erythematosus.

Purpose: Clinically significant valvular heart disease due to systemic lupus erythematosus (SLE) has generally been considered rare, and Libman-Sacks endocarditis has been thought to be predominantly an autopsy finding. With the declining prevalence of rheumatic heart disease, however, the spectrum of valvular heart disease is changing. We retrospectively analyzed our experience with SLE between 1975 and 1987 for the presence of hemodynamically significant valvular heart disease.

Pneumatosis cystoides intestinalis and benign pneumoperitoneum in a patient with antinuclear antibody negative systemic lupus erythematosus.

A patient with antinuclear antibody (ANA) negative systemic lupus erythematosus (SLE) developed pneumatosis cystoides intestinalis and spontaneous pneumoperitoneum. The literature of pneumatosis cystoides intestinalis and spontaneous pneumoperitoneum is reviewed, the benignancy of these conditions is emphasized, and particular attention directed to their association with and implications in the collagen vascular diseases. This is the first reported case of pneumatosis cystoides intestinalis and pneumoperitoneum in a patient with ANA negative SLE.

Radiographic assessment and psychologic variables as predictors of pain and functional impairment in osteoarthritis of the knee or hip.

Sixty-five outpatients with osteoarthritis of the knee and/or hip were assessed using radiographic ratings of disease severity, measures of psychologic coping, and multidimensional clinical outcomes of degree of pain and functional impairment. Disease severity accounted for little of the individual variability in clinical outcomes. Even after controlling for disease severity, psychologic variables remained strong predictors of individual differences in functional impairment and pain.

Gouty arthritis of the axial skeleton including the sacroiliac joints.

We treated a 62-year-old man with intermittent polyarthritis whose neck pain was prominent. Progressive deformities, limited neck motion, and the appearance of subcutaneous nodules prompted his admission to the hospital. The diagnosis of gout was established; the erosive and destructive changes in C6-7 were believed to be due to gout as well.

Analysis of restriction fragment length polymorphisms in rheumatic diseases.

Considerable evidence indicates that genes residing within the major histocompatibility complex (MHC) influence susceptibility to certain rheumatic diseases, such as ankylosing spondylitis (AS) and rheumatoid arthritis (RA). However, it has not yet been possible to precisely identify the gene(s) responsible for conferring enhanced susceptibility to these diseases. The availability of recombinant DNA technology should accelerate progress in obtaining this goal.

Association of a 9.2-kilobase Pvu II class I major histocompatibility complex restriction fragment length polymorphism with ankylosing spondylitis.

We analyzed DNA restriction fragment length polymorphism (RFLP) in 53 white ankylosing spondylitis (AS) patients and 92 healthy controls, utilizing a full-length HLA-B7 complementary DNA probe. A 9.2-kilobase (kb) Pvu II fragment was found to be significantly increased in frequency in B27 positive AS patients compared with the B27 positive control group (P = 0.

Evidence that autoimmunity in man is a Mendelian dominant trait.

Family studies of autoimmune diseases are consistent with multifactorial etiology. However, familial occurrence of the autoimmune trait as defined by the presence of autoimmune disease and/or high titer autoantibody supports the hypothesis that autoimmunity is inherited as an autosomal dominant trait. Based on genetic analysis of 18 autoimmune kindreds, the population frequency of this primary autoimmune gene is approximately .

Null alleles of the fourth component of complement and HLA haplotypes in familial systemic lupus erythematosus.

Eight families (121 individuals) with two or more members affected with systemic lupus erythematosus (SLE) were analyzed for histocompatibility antigens (HLA-A, B, C, DR, MT, and MB) and complement antigens (C4A, C4B, and BF). These data were correlated with serological markers (antinuclear antibodies, single- and double-stranded anti-DNA, anti-SM, anti-nRNP, anti-Ro [SS-A], anti-La [SS-B], and biological false-positive tests for syphilis and clinical features. Fifteen members had SLE, and 19 had other immune diseases (subacute cutaneous lupus erythematosus, discoid lupus erythematosus, hypothyroidism, insulin-dependent diabetes mellitus, primary Sjogren's syndrome, immune thrombocytopenic purpura, rheumatoid arthritis, and multiple sclerosis).

Primary Sjögren's syndrome and other autoimmune diseases in families. Prevalence and immunogenetic studies in six kindreds.

The relationships of human leukocyte antigen (HLA) and heavy chain immunoglobulin (Gm) haplotypes to disease and autoantibody expression were examined in six large kindreds, each having one or more members with primary Sjögren's syndrome. Various other autoimmune diseases and autoantibodies occurred among the 117 relatives in these families. The HLA and Gm haplotypes did not necessarily segregate persons into those with Sjögren's syndrome, other autoimmune disorders, or serologic abnormalities, but HLA alleles DR3 and DR2 occurred in significant excess in relatives with Sjögren's syndrome, irrespective of HLA haplotype.