O. Scherak

Lung Involvement in Rheumatoid Factor-negative Arthritis

Bronchoalveolar lavage (BAL) was performed on 13 asymptomatic patients with sero (rheumatoid factor)-negative arthritis (SNA); (6 with peripheral psoriatic arthritis, 2 with axial psoriatic arthritis, 3 with ankylosing spondylitis, 2 with sacroiliitis). BAL revealed a significant decrease of neutrophil granulocytes and an increase of B-lymphocytes in patients with SNA in comparison with 64 patiénts with rheumatoid arthritis (RA; 24 seronegative, 39 seropositive) and 15 healthy controls. Patients with SNA and RA had a significant increase of lymphocytes, especially T, T-helper and activated cells. In addition patients with RA had a significant increase of natural killer cells and a lower percentage of alveolar macrophages and T-suppressor cells. Transbronchial biopsy was performed on 9 patients with SNA and on 59 patients with RA. Abnormal histologic features of lung tissue were observed in 4 out of 9 patients with SNA (2 with fibrosis, 1 with follicular lymphoid hyperplasia, 1 with desquamative interstitial pneumonitis). The abnormal lung histology in RA patients was more pronounced, however, the differences between SNA and RA were not significant. The data from BAL and histology suggest, that the pulmonary involvement in SNA and RA is caused by an unspecified immunologic process.

Bronchoalveolar lavage in rheumatoid arthritis and secondary Sjögren's syndrome.

Bronchoalveolar lavage (BAL) was performed to investigate pulmonary involvement in 39 patients with rheumatoid arthritis (RA) and in 7 patients with RA and secondary Sjögren’s syndrome, and compared to 12 healthy controls. Lymphocytosis (more than 15%) was seen in 25, and more than 3% neutrophil granulocytes in 8 of 39 patients with RA. Lymphocytosis and/or neutrophil granulocytosis was seen in both seropositive and seronegative patients irrespective of clinical or radiologic findings. Patients with RA with or without secondary Sjögren’s syndrome had increased DR + lymphocytes in BAL compared with peripheral blood. In 7 patients with secondary Sjögren’s syndrome an increased helper/suppressor cell index (OKT4 + / OKT8+: 7.65 ± 2.10) and increased natural killer cells (OKNK +: 27.3 ± 5.5%) were found, as compared to 39 other patients with RA (OKT4+ / OKT8+: 2.16 ± 0.33, p<0.05; OKNK+: 14.5 ± 2.3%, p<0.05).These BAL data are further evidence of frequent subclinical interstitial pulmonary involvement in RA with differences in the active autoimmune process from those in secondary Sjögren’s syndrome.

HLA-DR antigens and disease patterns of rheumatoid arthritis

SummaryHLA-DR antigens were determined in 111 patients with classic or definite rheumatoid arthritis. HLA-DR4 was significantly (P corr. <10−6) increased in patients with rheumatoid arthritis (54%) compared with controls (23.2%). HLA-DR 5 was decreased in rheumatoid arthritis (12.6% vs 26.4% of controls); however, the corrected P value was not significant. There were no significant differences with regard to various clinical, radiological and serological parameters between HLA-DR 4 positive and negative patients. However, a milder course of rheumatoid arthritis was observed in DR 7 positive patients: Patients with this antigen were associated significantly with seronegativity and low titers of IgM-rheumatoid factor. Despite a similar disease duration patients with DR 7 had a significantly lower number of joints with inflammatory arthritis (synovitic swelling with limitation of movement) and developed less frequently severe radiological changes as joint ankylosis than DR 7 negative patients. In addition to the well known association between rheumatoid arthritis and HLA-DR 4, our data indicate that HLA-DR 7 may have a protective effect on the course of rheumatoid arthritis.

A method to differentiate between anti-C1q antibodies and C1q-binding immune complexes using collagenase-digested solid phase C1q

A method for the detection of circulating immune complexes in the presence of autoantibodies to C1q is described. Solid phase C1q-digestion with bacterial collagenase results in the elimination of the collagen-like region of C1q. Binding of model immune complexes to this modified solid phase C1q is practically unaltered, while reactivity of anti-C1q antibodies is abolished by this procedure. In conjunction with an ELISA using the collagen-like region of C1q as antigen this modified C1q solid phase assay may be used to determine immune complexes and anti-C1q antibodies in the sera of patients with autoimmune rheumatic diseases.

Effect of Levamisole on Immunological Parameters in Patients with Systemic Lupus Erythematosus

Parameters of cell-mediated and humoral immunity were examined in 8 patients with clinically inactive SLE undergoing levamisole treatment. Lymphocyte transformation with PHA and PMW was temporarily increased in the first month of therapy; at the same time absolute numbers of peripheral blood lymphocytes, T cells and B cells increased slightly. However, these differences were not significant statistically. In 1 patient with a diminished percentage of T cells and an increased percentage of B cells, levamisole induced normalization. Antibodies to DNA decreased in 6 patients, while titres of ANA decreased only in one patient. Serum levels of C1q and C3 increased in 7 and 3 patients, respectively. Four patients were treated with levamisole for 12 months, during which time there was neither clinical exacerbation nor deterioration of renal function and the concomitant corticosteroid therapy could be reduced.

Concanavalin A-induced suppressor cell activity and in vitro immunoglobulin secretion in rheumatoid arthritis: correlation with clinical and immunological parameters.

SummaryConcanavalin A-induced suppressor cell activity was found moderately but significantly (P<0.05) decreased in RA patients treated with nonsteroidal antiinflammatory drugs (31±7% suppression) as compared to patients on remission-inducing drugs, such as gold, penicillamine, or chloroquine (51±6%) or to healthy individuals (50±6%). Also, lymphocytes from patients with antibodies to collagen mediated lower suppression (33±7%) than lymphocytes from patients without evidence for these autoantibodies (61±11%). No significant difference between patients and controls or between individual groups of patients were observed in regard to IgM and IgG secretion induced by pokeweed mitogen. Thus, although no indication for a severe derangement of regulatory cells in peripheral blood of RA patients could be observed in this study, a slight deficiency of ConA-inducible suppressor cells that may be reverted by remission-inducing drugs seems to be present in RA.

HLA-DR1-Positive patients suffering from rheumatoid arthritis are at high risk for developing mucocutaneous side effects upon gold therapy

Population studies suggest an association between RA and, depending on the ethnic background, HLA-DR1 and/or -DR4. One standard regimen for the treatment of RA is the use of gold compounds like SATM to arrest progression of the disease. In the present study, the immunogenetic background of RA patients developing side effects upon SATM treatment was determined. A total of 53 patients under SATM therapy were tested for their HLA-DRB and -DQ alleles by DNA typing; a significantly higher frequency of HLA-DR1 (p < 0.004, uncorrected) was observed in patients presenting with mucocutaneous side effects (MCT) when compared with patients without MCT. The RR was 6.85. Thus, HLA-DR1 seems to be a marker for the susceptibility of gold adverse reactions.

Dermatoglyphics and Systemic Lupus Erythematosus

Finger tip and palmar dermatoglyphics of 37 female patients with systemic lupus erythematosus (SLE) were compared to 100 female controls; patients and controls were native inhabitants of the Eastern part of Austria. SLE patients had a significantly higher frequency of low endings of line A on both hands, and-on the left hand-significantly more patterns in the fourth and fewer patterns in the third interdigitum. There was no association between these dermatoglyphic features and the HLA antigens (B8 an DRw3), which occurred most frequently in our SLE patients.

Comment on the paper HLA-DR antigens in rheumatoid arthritis

We read with interest the above-mentioned article of the Swiss collaborative study on HLA-DR antigens in rheumatoid arthritis (RA). We reported our experience in Austrian patients with RA in 1983 and 1985 [1, 2] and found results that were different to some extent. In contrast to the findings of the Swiss group, the frequencies of DR1 and DR7 were not abnormal in our RA patients. Our observation of a significantly decreased frequency of DR1 DRw6 (Table 1) in RA patients must be interpreted with caution because of the broad reactivity of the antisera against this antigen. DR2 In addition to the products of the DR fll gene, other class-II DR3 antigens were identified. The supertypic specificities DRw52 and DR4 DRw53 are encoded by the DR /32 gene and include crossDR5 reacting groups of DR antigens: DR3, 5, w6, w8 and DR4, 7, w9, DRw6 respectively. DQ wl-3 are products of the DQa and DQfl genes. DR7 Recently we have completed an evaluation of DRw52, DRw53 DRw52 b and DQwl-3 in our RA patients. These antigens were determined DRw53 b using a panel of antisera from the 8th and 9th International DQwl b Histocompatibility Workshops and employing the two-colourDQw2 b fluorescence method. The patient-selection criteria, statistical analysis, and other methods used have been previously described DQw3 b [1, 21 . The significant increase known to have occurred in the frequency of HLA-DR4 was accompanied by an increase in the occurrence of DRw53 and of DQw3 (Table 1). This is in accordance with the results of Collier et al. [3]. In addition, we observed a protective effect of DRw52 and DQwl; this is due to the lower frequency of DR5 and DRw6 in RA patients. Except for DR7 [1, 2] we found no association between the other DR antigens or the three DQw antigens and negativity for rheumatoid factor (RF). DRw52 and DRw53 showed no correlation with clinical and radiological parameters of disease. In contrast, DQwl-positive status was significantly associated with a more severe course of disease regarding the number of joints affected, radiologic joint manifestations, clinical activity, and treatment with cytotoxic drugs (Table 2). On the other hand, patients with DQw2 had less affected joints, more slowly progressing radiologic destruction, and lower RF titers (Table 2). These results are in accordance with our previous observations [1, 2] of an association between DR1 and severe rheumatiod arthritis and of a milder course in DR7-positive patients. However, the correlations between the above-mentioned parameters were stronger with DR1 (except for radiologic changes) and with DR7 than with DQwl and DQw2, respectively. Although the DQ locus is in linkage disequilibrium with DRill, it can be concluded that the disease pattern of RA is primarily influenced by these DR antigens and only secondarily * P<0.05 influenced by DQ antigens. ** P < 0.005 Table 1. Frequency of HLA-DR and HLA-DQ antigens in patients with rheumatoid arthritis (RA) (n=157) and controls (n = 160). RR = relative risk; NS = not significant

Chest X-Ray in Collagen Vascular Diseases

The diagnostic value of chest X-ray following the ILO standards was compared with bronchoalveolar lavage (BAL) and the histology of transbronchial forceps biopsy in 83 patients with collagen vascular