Rheumatoid factors in rheumatoid arthritis and vasculitis

Summary To study the occurrence of rheumatoid factors (RF) in relation to the activity of rheumatoid arthritis and the occurrence of vasculitis, RF of IgM, IgA, and IgG classes were measured in sera from 35 patients with definite or classic rheumatoid arthritis (RA) using ELISA. For 26 patients, the RF levels were studied longitudinally and compared with changes in the articular index. Although IgM RF was occasionally found in patients without RA, IgA and/or IgG RF were almost exclusively associated with RA. The titers of IgM, IgA, and IgG RF were significantly higher in sera from patients with clinically diagnosed rheumatoid vasculitis than in sera from patients without vasculitis. No significant correlation between changes in the articular index and changes in titer of any class-specific RF could be found for the group of RA patients as a whole. However, in individual patients, increases or decreases in IgM and IgG RF titer were significantly correlated with an increase or decrease in the articular index.     

Clinical significance of rheumatoid factor isotypes in seropositive arthritis

Summary In this cross-sectional study a comparison was made of rheumatoid factor (RF) isotypes in 203 RF positive patients with arthritis. Of these, 129 had rheumatoid arthritis (RA) and 74 a milder disease that would formerly have been classified as probable RA. The majority (74%) of the RA patients had elevations of two or three RF isotypes compared with only 34% of the patients with the milder form of arthritis. A striking feature was that combined elevation of IgM RF and IgA RF was found in 67% of the RA patients compared to only 20% of the patients with milder arthritis who most frequently had an isolated elevation of IgM RF (41%). RA patients with an isolated elevation of IgA RF were younger and had a shorter disease history than RA patients with an isolated elevation in IgM RF or a combined elevation of IgA RF and IgM RF. The prevalence of raised IgM RF was, furthermore, found to increase with age and disease duration. We concluded that a raised level of IgA RF is an adverse phenomenon in patients with seropositive arthritis while patients with an isolated increase in IgM RF may be expected to experience a relatively mild disease course.     

IgM rheumatoid factor (RF), IgA RF, IgE RF, and IgG RF detected by ELISA in rheumatoid arthritis.

One hundred patients with rheumatoid arthritis (RA), of whom 73 were seropositive by latex or Waaler-Rose (WR) assays, or both, 100 healthy subjects, and 102 diseased controls (22 patients with systemic lupus erythematosus (SLE) and 80 with bronchial asthma) were evaluated for the presence of IgM rheumatoid factor (RF), IgA RF, IgE RF, and IgG RF by an enzyme linked immunosorbent assay (ELISA). Ninety two per cent, 65%, 68%, and 66% of the patients with RA were found to be positive for IgM, IgA, IgE, and IgG respectively. A positive correlation existed between the levels of IgM RF and IgA RF on the one hand and disease activity on the other, and the levels of IgM RF and IgA RF correlated with the levels of circulating immune complexes as measured by a C1q binding assay. The presence of extra-articular features also correlated positively with the levels of IgA RF and IgE RF. Five out of six patients with Sjögren''s syndrome had very high levels of IgA RF. Of 47 patients typed for HLA-DR, DR1 and DR2 were significantly more frequent in those with the highest levels of IgM RF. Conversely, DR3 was associated with low levels or absence of IgA RF and IgE RF. These results suggest that immune response genes may regulate the level of different RF isotypes. The frequencies of IgM, IgA, IgE, and IgG RF were 59%, 36%, 9%, and 27% respectively in SLE and 25%, 2.5%, 70%, and 59% in bronchial asthma.     

Isotypes of rheumatoid factors in rheumatoid arthritis and chronic liver diseases

We studied isotype-specific rheumatoid factors (RFs) to clarify their significance in rheumatoid arthritis (RA) and to verify the difference in RF isotypes between RA and chronic liver diseases (CLD). Isotype-specific RFs in RA and in CLD were measured by enzyme-linked immunosorbent assay (ELISA). Most sera (n = 51, 94.1%) from RA patients contained some kind of RF isotypes (92.1% for IgM RF, 76.4% for IgG RF, and 43.1% for IgA RF), and seronegative RA by ELISA was seen in only 11.8% (n = 6). The most characteristic combination of RF isotypes in active RA was IgG, IgA, and IgM. This combination of RF isotypes changed to IgG plus IgM, according to the diminution of RA activity; then, we found only IgM RF in inactive RA. The titers of each RF isotype also decreased in parallel with the activity of RA. IgA RF seemed to be the most sensitive factor for evaluating the activity of RA. In CLD, almost the same high frequency (n = 49, 89.8% for IgM RF, 59.2% for IgG RF), with the same titer levels seen in RA, was observed. On the other hand, IgA RF was significantly lower in frequency (n = 9, 18.4%) and in titer, compared with the finding in RA. Surprisingly, even in CLD, true seronegativity by ELISA was also found in very few patients (n = 4, 8.1%). In CLD, positive RFs detected by agglutination assay were seen more often in chronic hepatitis than in liver cirrhosis. In RA patients, significant associations of IgA RF and the serum concentration of IgA, and IgG RF and the serum concentration of IgG, were observed. On the other hand, in CLD patients, significant associations of IgG RF and the serum IgG concentration, and of IgM RF and the serum IgM concentration, were observed. These results indicated that IgA RF in active RA is the most characteristic RF isotype distinguishing it from other nonrheumatic diseases, as well as from inactive RA. RF isotypes reflected the background polyclonal B-cell activation in different manners in both diseases. In CLD, RF isotypes seemed to be disease-related immunological disorders reflecting disease progression. Received: February 17, 2000 / Accepted: July 5, 2001     

Anti-CCP antibodies in rheumatoid arthritis and psoriatic arthritis

Our aim is to assess the prevalence and associated clinical features of anti-CCP (cyclic citrullinated peptide) antibodies for RF (rheumatoid factor)-positive and RF-negative rheumatoid arthritis (RA) and psoriatic arthritis (PsA). In a prospective, cross-sectional, multi-centre study, we determined the titres of anti-CCP antibodies in 208 RA patients (129 RF-positive, 79 RF-negative), 56 PsA patients and 39 healthy controls (HC). Clinical parameters including disease activity (disease activity score 28-DAS28), physical disability (health assessment questionnaire-HAQ), functional capacity (functional class) and radiological erosions were investigated in patients with RA. In PsA patients, clinical and radiological features were determined. Anti-CCP2 antibodies were measured using a second-generation anti-CCP enzyme-linked immunosorbent assay (Euro-Diagnostica, Netherlands). One-hundred four of 129 RF-positive RA (81%), 16 of 79 RF-negative RA (20%), seven of 56 PsA patients (12.5%) and none of the HC had anti-CCP antibodies. RA patients with anti-CCP antibodies had significantly higher disease activity, greater loss of function and more frequent erosive disease than anti-CCP antibody-negative group. In subgroup analysis, anti-CCP antibodies in RF-negative patients were also associated with erosive disease. All PsA patients with anti-CCP antibodies had symmetric arthritis with higher number of swollen joints. The prevalence of anti-CCP antibodies in RF-positive RA patients was significantly higher than in RF-negative RA and PsA patients. Anti-CCP antibodies were also associated with erosive disease in RF-negative RA patients. Both anti-CCP and RF tests were negative in 30% of the patients. Anti-CCP positivity was a frequent finding in PsA and associated with symmetrical polyarthritis.     

Population study of the importance of rheumatoid factor isotypes in adults.

Blood samples collected from 13,858 randomly selected subjects participating in a health survey in Iceland from 1974 to 1983 were tested for rheumatoid factor. Samples that were positive in a sensitive RF screening test were analysed further by the Rose-Waaler technique and an isotype specific enzyme linked immunosorbent assay (ELISA). In 1987 the 173 available participants who were RF positive and 156 matched RF negative controls were evaluated clinically for rheumatoid diseases. RF levels and isotype patterns were more persistent in the patients with rheumatoid arthritis (RA) than in RF positive subjects who did not have overt RA. The prevalence of RA was only 19% in the participants who were RF positive in 1987. Forty per cent of the participants who had a persistent (four to 13 years) increase of IgA RF combined with either IgM or IgG RF were diagnosed as having RA. A positive correlation was found between RF levels and various manifestations of RA. This association was stronger for the IgA and IgG RF isotypes than for IgM RF. Excluding RF positivity as a diagnostic parameter, RA was diagnosed in 33 of the participants and 20 (61%) of these patients had increased levels of IgM and IgA RF. Patients with RA with bone erosions in their hands had higher levels of IgA RF than patients without erosions, but an association was not found between bone erosions and other RF isotypes. None of the RF negative participants who were symptom free when the original blood sample was taken developed RA during the four to 13 year follow up period. In contrast, five symptom free RF positive participants developed RA during this period. These five patients had all had increased levels of at least two RF isotypes before the onset of their symptoms. It is concluded that the IgA and IgG RF isotypes have a closer association with the clinical parameters of RA than IgM RF. Furthermore, increases in RF can precede clinical manifestations of RA and this applies in particular to the IgA and IgG RF isotypes.     

Enzyme immunoassay of complement-binding rheumatoid factors

Summary We describe an enzyme immunoassay for the determination of complement-binding rheumatoid factors. Polystyrene tubes are coated with heat aggregated human IgG. The rheumatoid factors (RFs) of patients heat inactivated sera are allowed to bind to aggregated IgG and thereafter saturated with fresh human complement. The amount of C 3 complement bound is measured by indirect enzyme immunoassay. The levels of complement binding RFs were measured in 30 patients with seropositive rheumatoid arthritis (RA), in 19 patients with systemic lupus erythematosus (SLE), and in 30 healthy control subjects. Compared to the controls high levels of complement-binding RFs were found both in RA and in SLE (P<0.0005). The mean level of the complement binding RFs was higher (P<0.05) in active than in inactive SLE. Even though the 19 S IgM RF bound complement, in RA no correlation was found between the level of complement binding RFs and Waaler-Rose titre, but the level of complement binding RF correlated with the levels of nonagglutinating IgM RF (r=0.56, P<0.01) and IgG RF (r=0.70, P<0.001) that were obtained by enzyme immunoassay.     

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.     

Clinical significance of rheumatoid factors in early rheumatoid arthritis: results of a follow up study.

Serum rheumatoid factors (RF) were measured yearly in 135 women with rheumatoid arthritis by the Waaler-Rose and latex fixation tests and IgM, IgA, and IgG RF were measured by enzyme linked immunosorbent assays (ELISAs). The patients were followed up from an early phase of the disease for a mean duration of six years. Patients with a persistently positive RF test, irrespective of the type of test used, had more radiological abnormalities, more disease activity, worse functional ability, more extra-articular manifestations, and needed more treatment with second line drugs than patients with persistently negative or variably positive and negative test results during the follow up. Increased RF levels, especially a high level of IgA RF within three years of the onset of symptoms, was prognostic for a more severe disease outcome six years after the onset of symptoms.     

Synovial fluid levels of anti–cyclic citrullinated peptide antibodies and IgA rheumatoid factor in rheumatoid arthritis,psoriatic arthritis,and osteoarthritis

Objective

To assess the levels of anti–cyclic citrullinated peptide (anti‐CCP) and IgA rheumatoid factor (IgA‐RF) in synovial fluids of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and osteoarthritis (OA).

Methods

Knee effusions of 29 patients with RA (23 women, 6 men; mean ± SD age 60 ± 15 years), 20 with PsA (6 women, 14 men; mean age 51 ± 12 years), and 19 with OA (9 women, 10 men; mean age 73 ± 11.8 years) were aspirated, tested for white blood cell (WBC) counts, centrifuged, and stored at ?20°. Sera of 22, 11, and 12 of these patients with RA, PsA, and OA, respectively, were similarly stored. IgG anti‐CCP and IgA‐RF were detected by enzyme‐linked immunosorbent assay. Erythrocyte sedimentation rate and C‐reactive protein levels were used as measures of disease activity.

Results

Mean levels of synovial fluid anti‐CCP and IgA‐RF were significantly increased in RA joint effusions compared with PsA and OA (anti‐CCP: 150 ± 134, 34 ± 29, and 24 ± 26 units, respectively [P < 0.003]; IgA‐RF: 76 ± 77, 15.7 ± 10, and 18 ± 20 units, respectively). No significant difference was noted between OA and PsA. A significant correlation was found between synovial fluid anti‐CCP and serum anti‐CCP and IgA‐RF. In patients with RA, a significant correlation was found between synovial fluid WBC counts and IgA‐RF (P = 0.03) and serum IgA‐RF (P = 0.008), but not between synovial fluid and serum anti‐CCP levels. In RA patients, C‐reactive protein correlated with serum IgA‐RF.

Conclusion

Anti‐CCP and IgA‐RF were significantly increased in synovial fluid of RA in comparison with PsA and OA patients.

     

Immunoglobulin Binding Properties of the Prosorba Immunadsorption Column in Treatment of Rheumatoid Arthritis

Abstract: Studies of the humoral effects of the Prosorba column were conducted in conjunction with the Phase 3 trial of Prosorba versus sham therapy for rheumatoid arthritis (RA). When perfused with normal human plasma in vitro, Prosorba bound predominantly IgG with a maximal capacity of approximately 462 g of Ig per Prosorba column, equal to about 1.5% of circulating IgG. Prosorba treatment did not alter the concentrations of albumin, IgG, IgM, and IgA in 3 RA patients, except for a small dilutional effect. Kinetic studies demonstrated that Prosorba removed IgG > IgM, IgA, and IgM rheumatoid factor (RF) during the initial moments of apheresis and almost exclusively IgM RF after 15 min. No net protein removal occurred at 60 min. Mean values of circulating immune complexes (CICs) were not significantly decreased by 12 weekly treatments. Complement was activated by the apheresis system upstream of the Prosorba column without changing C3 or C4 levels. We conclude that the Prosorba mechanism of action in RA is not bulk removal of Ig, but might involve modification of the CIC repertoire and could include, but not be limited to, effects related to complement activation.     

ELISA determined IgM, IgG and IgA rheumatoid factors in rheumatoid arthritis and in other connective tissue diseases

We used an adaptation of an enzyme-linked immunoadsorbent assay (ELISA) to determine serum levels of IgM, IgG and IgA rheumatoid factors (RF) in 50 patients with classic or definite rheumatoid arthritis (RA) according to the ARA criteria, balanced for positive or negative-routine Latex-RF reaction. A control group of 50 young normal subjects and a reference group of 44 patients with other connective tissue diseases (OCTD) were also studied. We confirmed the high sensibility of the method, together with its good specificity and reproducibility. For the IgM RF a very significant correlation was found between ELISA results and Latex-RF titration (p less than 0.001). Many Latex-RF negative RA patients had high ELISA levels of IgM RF, suggesting that this assay reveals, at least in part, hidden or non-agglutinating IgM RF. Among the OCTD group only some SLE cases, mainly Latex-RF positive, had enhanced IgM RF on ELISA. Considered quantitatively, IgG RF did not play a significant diagnostic role for RA (p greater than 0.05), because they were also found, with widely dispersed values, in normal subjects, and because the mean increase in RA patients was relatively small. Interestingly, IgA RF were above the normal range in many RA patients, both Latex-RF positive or negative. The mean values differed significantly from those of controls (p less than 0.005), and a correlation was observed between IgA RF levels and IgA containing immune-complexes. Normal IgA RF values were observed in SLE patients, even if Latex-RF positive, suggesting that their increase in RA patients is not the mere expression of a polyclonal B cell activation.     

IgG and IgM rheumatoid factor in active seronegative nodular rheumatoid arthritis and in children with benign rheumatoid nodules

Summary Rheumatoid nodules in rheumatoid arthritis are usually associated with high levels of IgM rheumatoid factors and aggressive disease. IgM, IgG, and C3 have been identified in tissue sections of rheumatoid nodules, suggesting pathogenetic importance. The role of IgM and IgG rheumatoid factors in sero-negative RA is poorly understood. Seven patients with active seronegative RA and rheumatoid nodules and 10 seronegative children with the syndrome of benign rheumatoid nodules were studied for the presence of IgG and IgM rheumatoid factors by radioimmunoassay and for complement-fixing IgM rheumatoid factor by haemolytic assay. Elevated titres of hidden complement fixing IgM rheumatoid factor were found in 60 % of the patients with benign rheumatoid nodules studied but in none of the patients with active seronegative nodular RA. Serum IgG and IgM rheumatoid factor levels by radioimmunoassay and circulating immune complex levels in both groups were not significantly different from normal controls. These data suggest IgG and IgM rheumatoid factors do not participate in the pathogenesis of active seronegative rheumatoid arthritis with rheumatoid nodules.     

Cryoglobulins in cases of rheumatoid arthritis

Summary Clinically diagnosed cases with different grades of rheumatoid arthritis (RA) were studied for (a) cryoglobulin content (b) constituents of cryoglobulins, and (c) rheumatoid factor (RF) titers in sera and cryoglobulins. Of 60 patients, 28 (46.66%) had significantly high levels of cryoglobulins and were mainly distributed in the severe group. Significant amounts of IgG and IgM were found in the cryoglobulins of the 15 cases of RA studied. Ten of these cases had detectable C₃ in their cryoglobulins. Of 20 cases of RA, 10 had detectable levels of RF in their cryoglobulins, as shown by the latex agglutination method. There was no significant correlation between the RF titers of cryoglobulins and the RF titers in the corresponding sera or the quantity of IgM and IgG components in them. Since the RF titer in cryoglobulin seemed to indicate the severity of the disease, the use of this parameter is proposed for diagnosis and prognosis of RA.     

Anti-IL-8 autoantibodies and complexes in rheumatoid arthritis: polyclonal activation in chronic synovial tissue inflammation

The chemokine interleukin-8 (IL-8) is frequently associated with inflammatory diseases, and autoantibodies against IL-8 are present in the periphery at elevated levels in such conditions as rheumatoid arthritis (RA). Circulating free anti-IL-8 IgG autoantibodies correlate with inflammatory parameters and disease severity in RA. In this study, correlations were sought between these disease parameters and other antibody subclasses. We assayed IgM, IgA and IgG anti-IL-8 antibodies and IL-8 immunoglobulin immune complexes in the serum of 29 healthy controls and 56 patients with defined RA, and compared the results with clinical and humoral disease parameters. IgG and IgM antibodies directed against IL-8 were present in all samples. In the disease groups, all isotypes of free anti-IL-8 antibodies correlated with increasing humoral disease parameters like CRP and CIC and their related anti-IL-8 immune complexes. Samples which contained high titers of anti-IL-8 antibody subclasses and complexes were RF subclass-positive, while IgM RF-negative sera showed low levels of anti-IL-8 and complexes. Detectable levels of IgG and IgA RF were found in all sera. Patients with extra-articular organ manifestation showed significantly increased free IgA and IgA/IL-8 complexes, with no correlation to the IgA RF titer or IgA hypergamma-globulinemia. The highest titers were seen in two RA cases with vasculitis and in one patient with colitis. Polyclonal activation of the humoral antibody system, which normally precedes the resolution of an inflammatory response, can itself lead to secondary stimulation of inflammatory processes via immune complex formation. In the immune pathology of RA, it degenerates into a persistent chronic inflammation accompanied by progressive joint destruction. The presence of elevated IgA subclass anti-IL-8 autoantibodies in RA patients with extra-articular manifestations suggests these autoantibodies as a clinically useful marker of disease severity and extra-articular manifestations. Received: 10 June 1998 / Accepted: 5 October 1998     

Lymphocyte infiltration and the synthesis of IgM and IgA rheumatoid factors by rheumatoid synovial membrane

Summary IgM and IgA rheumatoid factor (RF) synthesis by synovial membrane mononuclear cells was measured in 14 patients with rheumatoid arthritis (RA). The results were compared with blood mononuclear cell cultures and correlated with the intensity of lymphocyte infiltration of the synovium. IgM RF was produced by all synovial cultures compared with 56% of blood cultures; IgA RF was produced by 86% of synovial cultures and by 21% of blood cultures. A correlation was observed between synovial IgM RF synthesis, but not IgA RF synthesis, and the intensity of T cell and B cell infiltration of the synovial membrane.     

Class specific rheumatoid factors in rheumatoid arthritis: response to chrysotherapy and relationship to disease activity

IgG rheumatoid factors (RF) may play an important role in the pathogenesis of rheumatoid arthritis (RA). Our study investigates the relationship between class specific RF levels measured by radioimmunoassay and disease activity in patients with RA undergoing chrysotherapy. Nineteen patients were treated with 20 mg disodium aurothiomalate weekly for 6 months. Rheumatoid disease activity was assessed before and after 6 months' treatment and the level of IgG, IgA and IgM RF measured. There were significant falls in disease activity (p less than 0.005), IgA RF (p less than 0.005) IgG RF (p less than 0.005) and SCAT (p less than 0.025), but not IgM RF, over the 6 month treatment period. No correlation was found between absolute levels of IgA, IgG or IgM RF and disease activity before or after 6 months' therapy but there was a highly significant linear correlation between reduction in IgG RF levels and fall in disease activity (r = 0.642, p less than 0.005) with treatment.     

Rheumatoid factor by laser nephelometry and Waaler-Rose assay: prognostic value in patients with recent-onset rheumatoid arthritis

OBJECTIVE: To evaluate the prognostic value of rheumatoid factor (RF), detected in the Waaler-Rose agglutination assay and by nephelometry, in patients with recent-onset rheumatoid arthritis (RA). METHODS: Consecutive patients with new-onset RA between 1993 and 1997 were followed for a median period of 4.7 years. Clinical data at baseline and drug use during the disease course were recorded. Outcome parameters studied were disease process, damage (erosions, joint surgery, extra-articular manifestations, and new co-morbidity), and death. Cut-off levels for RF were >40 IU/mL (nephelometry) and titres 1:160 (Waaler-Rose haemagglutination). RESULTS: RF tests were negative by both methods in 22% of RA patients (RF- group), while 33% were RF positive by nephelometry only (RF+ group) and 45% were positive by Waaler-Rose and nephelometry (RF++ group). Baseline clinical and laboratory findings as well as the number of subsequently used disease-modifying anti-rheumatic drugs (DMARDs), the number of patients starting and the time spent on steroid therapy were similar in the three RF groups. Odd ratios for death (n = 23), erosions (n = 62), and serious extra-articular disease manifestations (EAMs) (n = 13) as well as patient survival, erosion-free or surgery-free survival rates did not differ between the RF groups. Only rheumatoid nodules were more frequent in RF++ patients. CONCLUSION: The baseline presence of RF by either Waaler-Rose or nephelometry was not associated with differences in drug therapy, morbidity other than rheumatoid nodules, or mortality in RA patients in the first 5 years of disease. Being immunoglobulin M (IgM) RF positive thus had little impact on RA patient outcome.     

Rheumatoid factor isotypes and circulating immune complexes in rheumatoid arthritis

Solid phase enzyme immunoassays were here used to quantify rheumatoid factors (RF) of the IgM, IgG and IgA classes and the immune complexes (IK) by their ability to bind to C1q or conglutinin in both the serum and synovial fluid of patients with rheumatoid arthritis (RA). Elevated serum levels of any RF isotype could be found in all patients with seropositive RA (IgM: 63%, IgG: 87%, IgA: 90%). Seronegative patients with RA presented to a significantly lesser extent with elevated levels of all the RF isotypes tested (IgM: 0%, IgG: 40%, IgA: 32%). Synovial fluid RF levels were significantly higher in SPRA patients than in SNRA patients with the exception of IgG-RF. All of the RF classes in both RA groups, however, were elevated when compared to RF in the synovial fluid of patients with osteoarthrosis. Both C1q binding and conglutinin binding immune complexes were significantly higher in the synovial fluid than in the serum of RA patients. The erythrocyte sedimentation rate and plasma iron levels were correlated with the levels of C1q binding immune complexes (IC) in the synovial fluid; total iron binding capacity showed an inverse relationship to synovial fluid IgG-RF levels. A radiographic index was also correlated with IgG-RF levels in the synovial fluid. Extraarticular manifestations were significantly more frequent in patients with elevated serum levels of IgM-RF or conglutinin binding IC. These findings indicate that IgG-RF in the synovial fluid and the formation of IC determined by their ability to bind C1q seem to be closely related to clinical features of local disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prospective study of early rheumatoid arthritis. II. Association of rheumatoid factor isotypes with fluctuations in disease activity.

Thirty-three patients with early peripheral synovitis were followed up for two to four years in order to study the relationship between fluctuations in rheumatoid factor (RF) levels and indices of clinical activity. Twenty-eight of these patients developed classical/definite rheumatoid arthritis (RA). Seventeen patients developed erosive disease of their hands and wrists and thirteen had a positive RF agglutination test. Nineteen patients had raised levels of IgM, RF, IgA, RF, or IgG RF as measured by isotype-specific ELISA techniques. The within-patient fluctuations in IgA RF levels correlated significantly with the corresponding fluctuations in grip strength (p less than 0.05), erythrocyte sedimentation rate (ESR) (p less than 0.01), and a composite index of disease activity (p less than 0.02). IgG RF levels were also associated with changes in ESR and grip strength, but IgM RF showed only a weak association with fluctuations in ESR and not with any other clinical parameters. It is suggested that serum IgA RF may be a useful marker of disease activity in rheumatoid arthritis.