The association of HLA-DR4 antigen with juvenile chronic arthritis and slipped capital femoral epiphysis.

Seventeen children who met the criteria for juvenile chronic arthritis (JCA) were reviewed. Throughout the study, the clinical examination, HLA phenotyping, and radiological assessment of the hips were performed by separate authors who were blinded to other data. At the end of the study, the results were also compared with 25 healthy, age- and sex-matched children. Six of the children with JCA also had radiological signs of slipped capital femoral epiphysis (SCFE; five with minimal slip pattern, one with moderate slip), and five of them had DR4 in their genotypes, in contrast to the remaining 11 patients who did not (p < 0.001). On the other hand, only 2 of 25 children in the control group had DR4 (p < 0.01). The difference was not significant when the patients without SCFE were compared with the control group (p = 1.0). The relative risk of cases with DR4 antigen for SCFE was 57.5, while it was below I for the other antigens. These results suggest that although DR4 is not specific for JCA, it is the common HLA antigen for those who have SCFE, and patients with JCA and HLA-DR4 antigen should be examined for evidence of SCFE, which was not reported before to exist with JCA.

A common HLA phenotype in slipped capital femoral epiphysis?

Studies from three different countries have linked the HLA B12 and DR4 antigens with slipped capital femoral epiphysis (SCFE). We questioned whether our patients shared in common either of these antigens. HLA phenotype was determined in 7 patients with SCFE, two of whom were brothers with almost identical haplotypes. The B12 antigen was found in none of our patients and the DR4 in only 3. Neither of the 2 brothers held the DR4 antigen. The commonest antigens (also shared by the 2 brothers) were B35, present in 5 and DR52 in 4 of 7 patients. We conclude that neither the previously described B12 nor the DR4 antigen can reliably serve as genetic markers for SCFE in our region.

The HLA phenotype in slipped capital femoral epiphysis.

The HLA genotypes of six patients with acute grade I slipped capital femoral epiphysis as determined by microlymphocytotoxic technique revealed HLA-DR4 as their phenotypes. These results contradict the previously reported HLA-B12 as the phenotype of patients with slipped capital femoral epiphysis.

Localised immune complexes and slipped upper femoral epiphysis.

Slipped upper femoral epiphysis remains a disease of unknown aetiology. Recent evidence has bolstered speculation that the immune system may play a role in the aetiology or pathogenesis of slipped epiphysis or of one of its complications, chondrolysis. This study reports the finding of immune complexes in the synovial fluid of all but one hip affected with slipped epiphysis in a consecutive series. In seven patients, immune complexes were detected by both the Raji cell assay and C1q-binding assay; in two, by the C1q-assay only; and in one, by the Raji cell assay only. No patients had immune complexes in the serum. Twenty-one patients with synovitis of the knee or hip caused by a variety of disorders served as the control group. Two of these patients had immune complexes in their synovial fluid. It appears that the immune complexes characterise the synovitis found with slipped upper femoral epiphysis as distinct from most other synovitides.

Synovial immunofluorescence in patients with slipped capital femoral epiphysis.

To evaluate if the immune system is active in slipped capital femoral epiphysis (SCFE) or chondrolysis, 16 patients with SCFE were studied by evaluation of their serum immunoglobulins, histology of their synovium, and immunofluorescent staining of their synovium. Patients with Perthes' disease, chondromalacia patellae, septic arthritis, sickle cell disease, and torn meniscus were controls. Serum immunoglobulins were normal in all patients. The histology demonstrated synovitis in all patients except in one normal knee. Plasma cells were a prominent feature of the synovitis in the patients with SCFE. Three patients had positive synovial immunofluorescence for IgG and C3. Two of these patients subsequently developed chondrolysis and one did not. One additional patient who had negative synovial immunofluorescence developed chondrolysis. It is postulated that the immune system is active in some patients with SCFE, but what, if any, role it plays in the disease or its complications remains to be shown.

Biochemical abnormalities in patients with slipped capital femoral epiphysis and chondrolysis.

A prospective clinical and laboratory study was performed in thirty-four patients (twenty-two blacks, ten Puerto Ricans, and two whites) who had slipped capital femoral epiphysis in fifty-two hips. Although the majority of the laboratory studies were normal, all patients showed significant elevations of the serum immunoglobulins and C3 component of complement, with the highest values recorded for IgA. Urinary glycosaminoglycans were elevated in the few patients studied and increased proportionally with the duration of the disease. Nine (25 per cent) of the thirty-four patients had chondrolysis in thirteen hips. The male:female ratio in these nine patients was 0.8:1, compared with the ratio of 1.4:1 in all thirty-four patients. No additional biochemical abnormality was found in the patients with chondrolysis except for a greater elevation of the IgM fraction. These preliminary and tentative data suggest either that slipping of an epiphysis produces an antigen which induces an autoimmune state or that slipping is a localized manifestation of a generalized process resembling some form of connective-tissue disorder or inflammatory state. There is presumably a genetically determined sub-group of patients with this disorder who may have chondrolysis.