Immunogenetic studies of juvenile dermatomyositis. III. Study of antibody to organ‐specific and nuclear antigens

Abstract

Ninety children with definite juvenile dermatomyositis (JDMS), who had been HLA typed, were tested for the presence of tissue or organ‐specific antibodies. Sixty had active disease at the time of study. The mean disease duration was 4 years, and 30 had soft tissue calcifications. The following autoantibodies were sought: thyroid, gastric parietal cells, smooth muscle, striated muscle, microsomes, mitochondria, DNA, extractable nuclear antigen, Sm, PM‐1, antinuclear antibody (ANA), and rheumatoid factor. Only the ANA and PM‐1 were more frequent in patients than in controls (P < 0.0002 and P < 0.001, respectively). Higher levels of immune complexes (P < 0.01) were found in sera from patients with JDMS than in sera from controls and were correlated with the presence of ANA in patients (P < 0.01). Soft tissue calcification was not associated with any autoantibody or HLA antigen, but with disease duration and activity (P < 0.001 and P < 0.05, respectively). There was no association between the occurrence of any autoantibody and the presence of HLA‐B8 or DR3 among the white patients with JDMS. The frequency of autoantibodies in 43 full siblings of children with JDMS was not increased. We conclude that children with JDMS, with or without HLA‐B8/DR3, do not show evidence of a generalized nonspecific antibody response to tissue antigens. The significance of the increased antibody to nuclear antigens ANA and PM‐1 remains to be determined.

Decreased Levels of CD54 (ICAM-1)-Positive Lymphocytes in the Peripheral Blood in Untreated Patients with Active Juvenile Dermatomyositis

“…In addition to the increase in B cells, over 70% of active untreated JDM patients have a positive anti-nuclear antibody test and selected (not polyclonal) elevation in Ig levels (22,24). The peripheral lymphopenia and the relative increase in the percentage of B lymphocytes may be associated with a decrease in circulating CD8 ϩ cells, with increased localization of CD8 ϩ lymphocytes in the affected muscle (23); however, intrinsic B-cell activation has not been investigated.…”

Prevalence of Coxsackie B Virus Antibodies in Patients With Juvenile Dermatomyositis

“…The study population consisted of 12 children with definite JDM (as defined above), who had been observed in the rheumatology clinic of Children's Memorial Hospital, Chicago (17)(18)(19)(20)(21)(22)(23). These children, whose ages ranged from 3-11 years (mean 7.0), had been extensively evaluated (17)(18)(19)(20)(21)(22)(23). They were not admitted to this phase of the study unless their date of disease onset was sharply identified and unless peripheral blood samples had been obtained within 4 months of disease onset, and promptly separated and kept frozen at -70°C for serologic investigations.…”

“…These observations suggested that coxsackie B viruses might be involved in the pathogenesis of JDM. To assess this possibility, we tested for antibodies to coxsackie B and other implicated viruses in serum samples from an extensively studied group of children with definite JDM (17)(18)(19)(20)(21)(22)(23) and from 2 groups of controls.…”

Gene Expression Profiling in DQA1*0501+ Children with Untreated Dermatomyositis: A Novel Model of Pathogenesis

“…The expression profiles do not distinguish between an active infection in the biopsy and a hit-and-run mechanism in which an infection initiates a cascade that persists after the active organism has been cleared. Genes involved in Ag presentation may hold clues to this issue, because the majority of JDM patients have consistent evidence of a very limited spectrum of autoantibodies (11)(12)(13). Genes controlling the early phase of Ag presentation were up-regulated in JDM; they include MHC class II proteosome elements LMP2 (6-fold higher) and LMP7 (ϳ42-fold higher) and Ag transporter TAP1 (also called RING4, up ϳ37-fold), which presents Ags to CD8 ϩ T cells (common in JDM muscle).…”

“…For example, Ig is deposited on muscle fibers in association with the membrane attack complex (10). Although a majority of JDM sera contain a speckled pattern antinuclear Ab of unknown specificity (11), and a subset of these sera have Ab to a 56-kDa nuclear protein (12), which is more frequent in DQA1*0501-positive children with JDM (13), Ab-dependent cell-mediated cytotoxicity has not been demonstrated (14). Peripheral blood from untreated JDM demonstrates a lymphopenia, with a selective decrease in the CD8 ϩ subset as well as ICAM-I-positive non-CD19 ϩ cells (presumed T cells) (15).…”