ABSTRACT
We studied the occurrence of autoimmunity to articular antigens in 39 patients with noninflammatory osteoarticular syndromes and 60 controls. Cell mediated immunity (CMI) was measured by assaying for leukocyte inhibitory factor (LIF) in supernates of mononuclear leukocytes cultured with native human collagen (types I, II, or III) or proteoglycan monomer. After stimulation with type II collagen, but not other antigens, 27/39 patients and 13/60 controls had positive LIF assays (p less than 0.001). In controls, but not in patients, CMI was associated with positivity for the HLA antigen DR4. No patient had antibodies to native type II collagen. These findings may reflect normal responses to articular injury or suggest that CMI contributes to the pathogenesis of osteoarticular syndromes. But they also emphasize that peripheral blood reactivity is not a certain reflection of synovial immunopathology.
Subject(s)
Autoantibodies/analysis , Collagen/immunology , Joint Diseases/immunology , Joints/metabolism , Adolescent , Adult , Child , Child, Preschool , Collagen/classification , Collagen/metabolism , Female , HLA-DR4 Antigen , Histocompatibility Antigens Class II/analysis , Humans , Joint Diseases/metabolism , Male , Middle Aged , Reference Values , SyndromeABSTRACT
The HLA type of patients with various kinds of immune reactions to bovine collagen implants were evaluated to determine a possible genetic basis for such responses. All patients suffering adverse clinical reactions to bovine collagen implants were lacking the HLA-DR4 antigen. All patients who received multiple bovine collagen injections without having adverse clinical reactions were lacking HLA-B5 and HLA-DR5 and had a significantly increased incidence of HLA-DR4. Combinations of histocompatibility antigens may influence immune response to bovine collagen implants.
Subject(s)
Collagen/immunology , Genes, MHC Class II , HLA Antigens/immunology , Histocompatibility Antigens Class II/immunology , Prostheses and Implants/adverse effects , Animals , Cattle , Epitopes , HLA Antigens/genetics , HLA-B Antigens , HLA-DR4 Antigen , HLA-DR5 Antigen , Histocompatibility Antigens Class II/genetics , Histocompatibility Testing , HumansABSTRACT
Although it is clear that the major histocompatibility complex is associated with lymphocyte glucocorticoid sensitivity in mice, there has been less evidence for a similar relationship in man. We have typed 158 individuals for: (1) 13 A locus and 16 B locus antigens, (2) degree of stimulation of their purified lymphocytes by phytohemagglutinin A (PHA), and (3) degree of inhibition of the PHA stimulation by prednisolone and prednisolone-21-hemisuccinate. In contrasts of individuals with a particular antigen (homozygous or heterozygous) with all remaining individuals, HLA-B7 was found to be associated with an enhancing effect on the log stimulation by PHA while other antigens of these series did not have significant associations. In similar contrasts, A10 was associated with a decrease in sensitivity to glucocorticoid inhibition of PHA stimulation as measured by the log I50 of the suppression of PHA stimulation. Other antigens of these series were not found to have significant associations with the glucocorticoid sensitivity of lymphocytes in this assay.
Subject(s)
HLA Antigens , Lymphocyte Activation/drug effects , Prednisolone/pharmacology , Adolescent , Adult , Child , Child, Preschool , Female , Genes, MHC Class I , Humans , Male , Middle Aged , Phytohemagglutinins/pharmacology , Prednisolone/analogs & derivativesABSTRACT
Significant HLA-DR and MT associations were observed with certain clinical and serologic manifestations of pauciarticular onset juvenile rheumatoid arthritis (PO-JRA). An increase in the MTI frequency was found in 56 children with PO-JRA in comparison to 95 normal controls. This association was limited to children with a younger age of onset (less than 6 years) and a persistent pauciarticular course. An increase in HLA-DRW8 and a decrease in DR4 were associated with a younger age of onset and antinuclear antibody (ANA) seropositivity. In addition, an increased frequency of DR5 was seen in ANA positive children. All of these HLA-DR and MT associations were independent of coassociating Ia specificities.
Subject(s)
Arthritis, Juvenile/immunology , Histocompatibility Antigens Class II/analysis , Antibodies, Antinuclear/analysis , Arthritis, Juvenile/blood , Arthritis, Juvenile/classification , Arthritis, Juvenile/complications , Child , Child, Preschool , Female , HLA Antigens/analysis , HLA Antigens/classification , HLA-A Antigens , HLA-B Antigens , HLA-DR Antigens , Humans , Male , Uveitis/complicationsABSTRACT
One hundred fifty-nine individuals were typed for HLA-A and B antigens and levels of isoproterenol-stimulated, lymphocyte cAMP. No significant age, sex, or caffeine effects on the natural log of the lymphocyte cAMP variable (ln cAMP) were found. A comparison of mean ln cAMP levels between individuals who carried a particular antigen (homozygous or heterozygous) and individuals who did not carry the antigen identified a highly significant decrease in ln cAMP levels associated with the HLA-B18 antigen. We estimated that 18.9% of the variability in ln cAMP was attributable to the HLA-B18 antigen. In addition, 38% of the variability in ln cAMP was attributable to factors that aggregate in families that were independent of the HLA-B18 effect. A weaker association of A10 with lymphocyte cAMP might be due to linkage disequilibrium between A10 and B18.
Subject(s)
Cyclic AMP/genetics , HLA Antigens/genetics , Isoproterenol/pharmacology , Adolescent , Adult , Child , Child, Preschool , Cleft Palate/blood , Cleft Palate/genetics , Cyclic AMP/metabolism , Cystic Fibrosis/blood , Cystic Fibrosis/genetics , Female , Gene Frequency , Genetic Markers , Genetic Variation , HLA-A Antigens , HLA-B Antigens , HLA-B18 Antigen , Humans , Infant , Lymphocytes/metabolism , Male , Middle AgedABSTRACT
The analysis of the clinical and HLA profiles of 99 patients with Reiter's syndrome is reported. Antigen HLA-B27, which has previously been firmly associated with Reiter's syndrome, predisposes patients to develop disease features which reflect articular involvement. The HLA haplotype A2, B27 was found to be at an elevated frequency in our Reiter's syndrome sample, and the latter two antigens are also associated with a general increase in disease severity. Conversely, antigen BW35 appears to be protective against certain features of the syndrome. Patients with certain antigenic profiles (namely A2 and A3 together with B27) tend to develop certain syndrome manifestations earlier in the course of the disease than those with other antigens.
Subject(s)
Arthritis, Reactive/immunology , HLA Antigens/analysis , Humans , MaleSubject(s)
HLA Antigens/analysis , Migraine Disorders/immunology , Adult , Aged , Female , Humans , Male , Middle Aged , Migraine Disorders/geneticsABSTRACT
Mixed connective tissue disease (MCTD) was diagnosed in a brother and sister, and 18 additional family members spanning three generations were studied to detect evidence of autoimmune disease. Symptoms or signs of MCTD without complete expression of the disease were found in 8 relatives of the original cases. Antibodies to ribonucleoprotein and high-titer antinuclear antibodies were found only in the affected siblings. Tests for rheumatoid factor were positive in 9 of 17 relatives of the patients; the titers ranged from 1:160 to 1:2560. The brother and sister with MCTD had an identical HLA genotype--11,12/2,12. The same genotype was inherited by 3 of their siblings, who had impressive rheumatic complaints. This report emphasizes the association between inflammatory connective tissue disease and a specific HLA type within a single kindred.
