Effects of rheumatoid factor isotypes on disease activity and severity in patients with rheumatoid arthritis: a comparative study.

The value of rheumatoid factor (RF) isotypes for assessing rheumatoid arthritis (RA) remains debatable. In this study, we have examined the relationships between RF isotypes and disease activity and severity in RA patients. Sixty-two patients with RA, 48 women and 14 men, were studied. RF was measured by nephelometry (RF-N) and IgG-, IgA-, and IgM-RF isotypes were measured using enzyme-linked immunosorbent assay. Serum C-reactive protein and erythrocyte sedimentation rate were also determined. The patients were classified according to disease activity, joint damage, functional status, and presence of pulmonary involvement, rheumatoid nodule, and secondary Sjögren's syndrome. Although the patients with active disease had significantly higher IgA-RF and IgM-RF levels compared to inactive patients, IgA-RF and IgM-RF were not found to be independently associated with disease activity in multivariate analysis. In patients with severe joint damage, IgA-RF and RF-N were significantly higher than those of the other patients. Multiple regression analysis showed that IgA-RF was the unique variable independently associated to severe joint damage. The patients with class III and IV functional index had significantly higher IgM-RF, IgA-RF, and RF-N levels compared to the patients with class I and II functional index; however, RFs were not significantly associated with functional status in multivariate analysis. IgA-RF and IgM-RF were significantly associated with pulmonary involvement and rheumatoid nodule, respectively. No significant associations were found between RF isotypes and secondary Sjögren's syndrome. Our results suggest that the clinical usefulness of IgA and IgM isotypes is better than RF-N. Elevated IgA-RF may be a marker of erosive disease. The usefulness of RF isotypes for monitoring disease activity or functional status appears to be limited.

Serum-soluble Fas antigen level in patients with allergic rhinitis: its relation to specific immunotherapy.

There have been conflicting reports on the relationship between Fas/Fas ligand-mediated apoptosis and allergic response. Specific immunotherapy (SIT) is widely used for treatment of allergic diseases. It has long been apparent that SIT results in a reduction in antigen-specific lymphoproliferation, but it is unclear by what mechanism T-cell responses are inhibited by SIT in vivo. In this study, we examined serum-soluble Fas (sFas) levels in patients with allergic rhinitis and healthy subjects. We also examined the effect of SIT on sFas level. Seventy-two patients with allergic rhinitis and 20 healthy subjects were included in this study. Twenty-eight patients were newly diagnosed and 44 patients were treated with SIT for a 5-year or 7-year duration. Serum sFas levels were measured by a sandwich enzyme-linked immunoassay. Mean serum sFas level was 7931 +/- 2861 pg/mL in newly diagnosed patients with allergic rhinitis during the pollen season, 8426 +/- 2846 pg/mL in patients with allergic rhinitis treated by SIT for a 5-year duration, 8490 +/- 2256 pg/mL in patients with allergic rhinitis treated by SIT for a 7-year duration, and 7493 +/- 3450 pg/mL in healthy subjects. Serum sFas level was not found to be significantly different among the study groups (p > 0.05). These findings suggest that there is no relation between sFas level and the etiopathogenesis of allergic inflammation in patients with allergic rhinitis and mechanism of action of SIT.

Relationship between HLA-DR, HLA-DQ alleles and MEFV gene mutations in familial Mediterranean fever (FMF) patients.

BACKGROUND/AIMS: Three missense mutations clustered on the carboxyl-terminal portion of the MEFV gene (M680I, M694V, and V726A) have been observed in over 80% of affected alleles in several ethnic groups of familial Mediterranean fever patients. Several immunologic abnormalities were found both in cellular and humoral components in Mediterranean fever patients. Those observations have pointed the way for analysis of the HLA region in Mediterranean fever. We intended to compare HLA DR/DQ alleles with those major mutations in the MEFV gene in Mediterranean fever patients. METHODS: The distribution of MEFV gene mutations and HLA-DR, HLA-DQ alleles were analyzed in 40 index Turkish Mediterranean fever patients, 28 family members and 42 healthy controls. M680I, M694V, and V726A mutations were studied by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) analysis. HLA-DR and DQ allele subgroups were studied using SSP-PCR technique. RESULTS: A total of 37 (92.5%) patients in 40 Mediterranean fever index patients were found to carry one of the three missense mutations. The HLA-DR4 allele frequency was significantly higher in the Mediterranean fever patient group. When comparisons were made between Mediterranean fever mutations and HLA allele frequencies, M694V mutation with HLA DR3, DR11/5 and DR 13/6 and M680I mutation with DR7 allele subgroups were statistically significant. DQ6/1, DQ7/3, and DQ8/3 allele with M694V, DQ2 allele with M680I, and DQ6/1 with V726A mutations were also statistically significant. CONCLUSIONS: Our results indicate a relationship between some HLA-DR/DQ alleles and MEFV mutations in Mediterranean fever patients. We suggest HLA-DR/DQ alleles and their role in the pathogenesis of Mediterranean fever need further analysis and comparative studies.

The Effects of Sulphasalazine on Urinary Excretion of the Hydroxypyridinium Crosslinks of Collagen in Patients with Rheumatoid Arthritis

Secondary osteoporosis is a feature of rheumatoid arthritis (RA). In recent years, several attempts have been made to develop specific markers for monitoring connective tissue metabolism in arthritic diseases. Our purpose, in this study was to assess pyridinium crosslinks (PYD and DPYD) excretion in relation to the activity of RA (changes related to sulphasalazine treatment). Fourty premenopausal female patients with active RA (mean age; 36.0 7.2 years), 20 postmenopausal women with active RA (mean age; 60.0 6.8 years), 23 postmenopausal women with OA (mean age; 56.1 6.6 years) and 17 premenopausal healthy subjects (mean age; 28.3 4.28 years) were enrolled in our study. All of the 40 premenopausal female patients with active RA were given sulphasalazine. The mean follow up period for these patients was 10.3 1.1 months. In all of these patients, urine samples were collected both in the active and in the inactive periods. Urine PYD and DPYD levels were measured by ELISA. Urine PYD levels were significantly higher in the active period (14.01 3.16 nmol/mmol cr) than in the inactive (8.25 4.23 nmol/mmol cr) period in patients with premenopausal RA (p 0.05). Urine PYD levels were significantly high in postmenopausal active RA patients (19.06 3.26 nmol/mmol cr) compared to premenopausal active and ind inactive, postmenopausal inactive RA patients, osteoarthritis and healthy controls. Urine DPYD excretion was similar in patients with premenopausal RA in the active (7.46 2.13 nmol/mmol cr) and inactive periods (5.08 0.87 nmol/mmol cr) (p 0.05). In active premenopausal RA patients, a correlation was found between PYD excretion and RAI, ESR, CRP and functional capacity (r=0.5729 p 0.01, r=0.5953 p 0.01, r=0.6125 p 0.01 and r=0.6232, p 0.01 respectively). But in the inactive period, no such correlation was was evident. In disease activity parameters did not correlate with DPYD excretion in either the active or the inactive period. As a result, urine PYD excretion was significantly high in patients with active RA. During sulphasalazine treatment, urine PYD levels decreased. This is attributed to improvement in bone destruction.