J. Jouquan

Chronic lymphocytic leukemic (CLL) cells secrete multispecific autoantibodies.

A subset of B cells expressing the CD5 marker, a 67 KD molecule, has been implicated in the pathogenesis of autoimmune disease. To study the immunoglobulin repertoire of CD5+ B cells we investigated chronic lymphocytic leukemic (CLL) cells, since the majority of the malignant clones express CD5. CLL were induced to secrete their IgM in vitro by phorbol 12-myristate 13-acetate (PMA) and the supernatants screened for binding to a panel of autoantigens. Twelve out of 14 CLL clones were autoreactive, binding to Fc of IgG, ssDNA, dsDNA, histones, cardiolipin, or cytoskeletal components. Many also bound to more than one antigen tested for, showing multispecificity. Our data suggest that a high proportion of CD5+ B cells are programmed to secrete multispecific autoantibodies.

CD5-expressing B lymphocytes in the blood and salivary glands of patients with primary Sjögren's syndrome

CD5, the human counterpart of Ly-1 molecules in the mouse, are detectable but weakly expressed on a minute fraction of circulating B cells. The number of CD5 + B cells in the blood of patients with Sjögrens syndrome was slightly higher than in control blood, but it became statistically significant after treatment of the cells with phorbol myristic acetate. These numbers were even higher in patients with homogeneous serum bands than in the others. A few scattered cells were stained with anti-human IgM antibody on salivary gland sections, and among them 5-10% were found to be positive for anti-CD5.

IgA-containing immune complexes in the circulation of patients with primary Sjögren's syndrome

IgA-, IgM- and IgG-containing immune complexes (CIC) were detected in 48, 19 and 12% of 52 patients with primary Sjögrens syndrome (SS), in 36, 38 and 56% of 45 patients with rheumatoid arthritis, and in 8, 5 and 3% of 40 normal controls. A high proportion of primary SS patients also had considerable amounts of serum IgA and elevated levels of IgA with rheumatoid factor (RF) activity. IgA-CIC and IgA-RF were more frequent (P less than 0.03 and less than 0.001) in the 27 primary SS patients with, than in the 25 without extraglandular manifestations. IgA-CIC could play a role in mediating the tissue injury associated with primary SS.

CD5 positive B cells in patients with rheumatoid arthritis: phorbol ester mediated enhancement of detection.

CD5 molecules present on human T cells are detectable but weakly expressed on some human B cells. We have increased the sensitivity of their detection by treating the B enriched cells with phorbol myristic acetate (PMA), a tumour promoting agent. The numbers of CD5+ B cells in the blood of patients with rheumatoid arthritis (RA) were higher than in control blood, and after PMA treatment this was statistically significant. CD5+ B cells were also increased in tonsils, lymph nodes, and spleens after PMA activation. There were no significant differences between the percentages of B cells carrying chi or lambda light chains in their expression of CD5 molecules in patients with RA.

Anti-Golgi Complex Autoantibodies in Patients with Primary Sjogren's Syndrome

Commencing with the monograph by Henrik Sjogren (1), a number of investigators have delineated the numerous aspects of sicca syndrome (2-5), since then referred to as Sjogrens syndrome (SS). This disorder is characterized by an infiltration of lymphocytes and plasma cells into the exocrine glands, with resultant xerostomia and keratoconjunctivitis sicca. It can occur alone (primary SS), or in conjunction with another autoimmune disease, such as rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE).Production of a variety of autoantibodies is one of the immunological hallmarks of the syndrome (6). Of particular interest is the anti-Golgi complex (AGC) antibody, first detected by Rodriguez et al. (7) in 1982. This description was refined and extended by Fritzler et al. (8), but surprisingly very little information is available about this autoantibody.

Nonorgan-specific autoantibodies in individuals infected with type 1 human immunodeficiency virus

Fifty-six human immunodeficiency virus-1-positive asymptomatic carriers were tested for the presence of a variety of nonorgan-specific autoantibodies. Antinuclear antibodies were detected in 34 sera, of which 27 were directed to the mitotic spindle apparatus and all were of the IgG isotype. Anti-Golgi complex, anti-centriole, and anti-vimentin antibodies were also present in 20.4, and 4 sera, respectively. Ten patients had less than 500 CD4-carrying T lymphocytes per cubic millimeter. Nine of them had more than one autoantibody. No correlation could be demonstrated between the number of autoantibodies and the level of serum immunoglobulins.

Comparison of labial and sublingual salivary gland biopsies in the diagnosis of Sjögren's syndrome.

This study was designed to compare labial and sublingual salivary gland biopsies in the diagnosis of Sjögrens syndrome (SS). Fourteen labial and 29 sublingual specimens were considered positive. There was a better correlation between infiltration of the ductal structure and the focus score in the sublingual salivary gland biopsy than in the labial salivary gland biopsy. Use of sublingual salivary gland biopsy as an additional diagnostic tool in SS is therefore suggested.

Relationship of interleukin-4 to isotypic distribution of anti-double-stranded DNA antibodies in systemic lupus erythematosus.

IgG subclasses of anti-double-stranded DNA antibodies were determined in 182 patients with systemic lupus erythematosus. All isotypes were detected, but IgG1 and IgG3 were predominant (62 and 51% of the cases, respectively). An average of 64 +/- 27% was IgG1, 16 +/- 22% IgG2, 16 +/- 19% IgG3 and 4 +/- 10% IgG4. The rank order or frequency was IgG1, IgG3, IgG2 and IgG4 in patients with musculoskeletal involvement; IgG1, IgG2, IgG3 and IgG4 in those with renal complications; IgG3, IgG1, IgG2 and IgG4 in those with cutaneous involvement; and IgG1, IgG3, IgG2 and IgG4 in those with hematological manifestations. Interleukin-4 (IL-4) was detectable in 17 of 36 selected patients, as opposed to 1 of 40 normal controls. The percentage of the total autoantibody contributed by IgG1 was significantly higher (p < 0.03) in these patients than in the remainder with undetectable levels of IL-4.

Relation of antivimentin antibodies to anticardiolipin antibodies in systemic lupus erythematosus.

Tests for antivimentin antibodies (AVA) were performed on 50 systemic lupus erythematosus (SLE) and 63 control sera by indirect immunofluorescence and enzyme linked immunosorbent assay (ELISA). The prevalence was significantly raised in SLE (38% and 50% of sera positive for IgM-AVA and IgG-AVA, respectively, by immunofluorescence; 36% and 64% of sera positive for IgM-AVA and IgG-AVA, respectively, by ELISA) in comparison with the control sera. A significant correlation existed between IgM-AVA, on the one hand, and anticardiolipin antibodies (ACA) and anti-single-stranded DNA (ssDNA), on the other. A stepwise principal component analysis demonstrated that IgM-AVA and IgG-AVA accounted for 71% of the total variance in SLE (50 patients x 5 parameters = total variance). Twenty ACA positive serum samples from patients with syphilis were therefore tested for the presence of AVA, but hardly any were found to be positive. IgM-AVA from patients with SLE were inhibited by cardiolipin and absorbed with ssDNA. An association between AVA positivity and arthralgia was also shown in SLE.

Nonorgan-specific autoantibodies and immunoglobulin allotypes in relatives of patients with monoclonal gammopathy.

Polyclonal immunoglobulin increase, rheumatoid factor, antinuclear antibodies and cold lymphocytotoxins were detected 10, 8, 7 and 8 times, respectively, in a group of these informative families (22, 17 and 29 subjects tested, respectively). Each family included at least 1 subject with a monoclonal gammopathy in addition to that of the proband. No correlation could be shown between any of these abnormalities and Gm haplotypes. Nonetheless, it is worth noting that 6 out of 41 relatives under 30 years of age had cold lymphocytotoxins.