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-linked immunosorbent assay (ELISA) screening test for detection of rheumatoid factor

Summary A new enzyme-linked immunosorbent assay (ELISA) screening test for total rheumatoid factor (RF) activity is described. Rabbit IgG was used as antigen and enzyme-conjugated monoclonal anti-kappa antibody as third layer. Of 183 samples measured for RF isotype levels, 60 were found to have one or more raised. In terms of raised isotypes the ELISA screening test had a sensitivity of 97% (58/60) while the Rheumaton had a sensitivity of only 75% (45/60). Nearly all discordant false-negative samples had only one RF isotype raised. The ELISA test gave 29% (53/183) and the Rheumaton 34% (63/183) false-positive results. Thus the ELISA test was more specific and sensitive for the detection of raised single RF isotypes than the Rheumaton and Rose-Waaler tests. Moreover, approximately 30% of RA patients were seronegative according to the conventional RF tests but only 8% in the new ELISA system.     

Combined elevation of IgM and IgA rheumatoid factor has high diagnostic specificity for rheumatoid arthritis

The diagnostic value of measuring rheumatoid factor (RF) by agglutination or isotype-specific enzyme-linked immunosorbent assay (ELISA) was compared. The study included 70 patients with rheumatoid arthritis (RA) and 205 patients with various other rheumatic conditions. Of the RA patients, 74% were RF-positive by agglutination and 90% had one or more RF isotypes elevated by ELISA compared to 14% and 22%, respectively, of the other patients. Strikingly, 70% of the RF-positive RA patients had an elevation of two or more RF isotypes compared to only 16% of the other RF-positive patients (P<0.0001). Furthermore, a combined elevation of IgM and IgA RF was found in 52% of the RF-positive RA patients, but only in two (4%) of the other RF-positive patients (P<0.0001). It is concluded that a combined elevation of IgM and IgA RF is highly specific for RA and is very rarely found in rheumatic diseases other than RA. Isotype-specific RF assays are therefore diagnostically superior to agglutination tests. The detection of the RA-specific RF isotype pattern may be particularly helpful early in the course of RA even before the disease is fully differentiated. Received: 10 December 1997 / Accepted: 25 June 1998     

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     

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.     

Elevation of only one rheumatoid factor isotype is not associated with increased prevalence of rheumatoid arthritis--a population based study

OBJECTIVE: To analyse the relationship between different rheumatoid factor (RF) isotype patterns and the prevalence of RA. METHODS: Serum samples, collected between 1973 and 1983 from nearly 14,000 randomly selected individuals, were screened for elevation of RF. In 1987, 173 RF positive and 156 matched RF negative participants were evaluated clinically. RESULTS: Participants with elevation of only one RF isotype, most commonly IgM, did not have significantly higher prevalence of RA than the RF negative controls. Of the 17 RF positive individuals who were diagnosed with RA, 14 (82%) had a combined elevation of IgM and IgA RF. CONCLUSION: In contrast to a combined elevation of IgM and IgA RF, elevation of only one RF isotype may not be a significant risk factor for the development of RA.     

The predictive value of rheumatoid factor isotypes, anti-cyclic citrullinated peptide antibodies, and antineutrophil cytoplasmic antibodies for mortality in patients with rheumatoid arthritis

OBJECTIVE: To evaluate the significance of rheumatoid factor (RF) and its isotypes (IgA RF, IgG RF, and IgM RF), anti-cyclic citrullinated peptide antibodies (anti-CCP), and antineutrophil cytoplasmic antibodies (ANCA) in predicting mortality in patients with rheumatoid arthritis (RA). METHODS: The study population comprised 604 patients with RA participating in a cross-sectional study in 1987. Presence of RF (n = 604), RF isotypes (n = 206), anti-CCP (n = 184), and ANCA (n = 200) were determined in these patients from available baseline sera. Vital status was assessed in 1999 and multivariate Cox regression analysis used to compare mortality in RA patients with or without different antibodies. RESULTS: Of the 604 patients with RA, 55% were positive for RF, 66% for anti-CCP, and 14.5% for perinuclear ANCA. Twelve patients (19%) with RF were anti-CCP-negative and 34 (40%) without RF were anti-CCP-positive. Of the total 604 patients, 160 had died by 1999. Positive RF and high IgA and IgM RF levels predicted increased mortality, while positive anti-CCP or ANCA did not. However, high anti-CCP levels were related to an increased mortality risk. CONCLUSION: Patients with RA with positive RF, especially IgA and IgM isotypes, carry a risk of dying earlier than patients without these serological findings.     

One year treatment with low dose methotrexate in rheumatoid arthritis: Effect on class specific rheumatoid factors

Summary We evaluated the effect of a one-year treatment of low dose methotrexate (MTX) on class specific rheumatoid factors in 27 patients with rheumatoid arthritis (RA). Enzyme-linked immunosorbent assay (ELISA) showed after 6 and 12 months a significant reduction of IgM-RF, IgA-RF and IgF-RF levels from the baseline values. During MTX treatment, changes of each RF isotype were not correlated with any other isotype and its corresponding immunoglobulin changes. Moreover, immunological changes were not related to the improvement of clinical parameters. Our results showed that low dose MTX can specifically affect levels of RF isotypes, which are involved in the immune pathogenesis of RA.     

Low mannose binding lectin predicts poor prognosis in patients with early rheumatoid arthritis. A prospective study

OBJECTIVE: To determine whether low mannose binding lectin (MBL) is associated with poor prognosis in rheumatoid arthritis (RA) and whether patients with RA have increased frequency of MBL deficiency. METHODS: Patients with recent onset symmetric polyarthritis (< 1 year, median 3 mo) were recruited if they had not been treated longer than 2 weeks with disease modifying drugs. They were reevaluated after 6 months and their disease activity and progression were correlated with their MBL concentration, rheumatoid factor (RF) isotypes, and C-reactive protein (CRP). Sixty-three female patients with advanced RA were also analyzed. RESULTS: Sixty-five patients with early arthritis fulfilled American College of Rheumatology criteria for RA and 52 were followed for 6 months or longer. Low MBL was associated with raised RF, IgA RF in particular (p = 0.02). and also with a combined elevation of IgM and IgA RF (p = 0.035). Patients with low MBL (lowest 25th percentile) showed less improvement after 6 months of treatment than patients in the highest MBL quartile. This applied to the Thompson joint score (p = 0.03) and grip strength (p = 0.004). Low MBL was also significantly associated with radiological joint erosions at recruitment and at 6 month followup (p = 0.039); and the group with advanced RA also showed a significant association between low MBL concentration and radiological damage (p = 0.036). However. neither patient group had increased frequency of MBL deficiency compared to healthy controls. CONCLUSION: Low MBL predicts poor prognosis in patients with early RA.     

Association of autoantibodies to filaggrin with an active disease in early rheumatoid arthritis

OBJECTIVE: To evaluate the clinical significance of antifilaggrin antibodies (AFA) measured by an enzyme linked immunosorbent assay (ELISA) in serial specimens from patients with recent onset rheumatoid arthritis (RA). METHODS: Filaggrin was purified from human skin and used as an antigen in ELISA. The AFA test was applied to five serial specimens from 78 patients with recent onset RA followed up for three years. Rheumatoid factor (RF) had been measured earlier from the same samples by quantitative immunoturbidimetry. RESULTS: The mean AFA level was highest at entry (54% positive), followed by a statistically significant decline at six months and a slight increase at three years. AFA were persistently positive in 23 patients and persistently negative in 28 patients. Eleven of the latter patients were persistently negative for RF. At study entry AFA levels correlated to some degree with RF levels. In general, raised AFA levels at entry were associated with an active and treatment resistant disease, but they did not predict radiological progression. CONCLUSIONS: The test for AFA has potential for an additional immunological test for RA.     

Prevalence of IgM, IgA and IgG rheumatoid factors in juvenile rheumatoid arthritis

Using an enzyme immunoassay, sera from 50 children with juvenile rheumatoid arthritis (JRA) and 39 controls were tested for IgM, IgA and IgG rheumatoid factors (RF). RF of the IgM and IgA isotypes were present in 11 (22%) patients, but in only one control (p = 0.008). IgG RF was present in the sera of 2 (4%) patients and in none of the controls (p = 0.21). Of the 22 patients with IgM RF or IgA RF, only 3 sera (14%) contained RF of both isotypes. IgM RF was more common in patients with polyarticular disease, while IgA RF was more common in patients with pauciarticular disease. These results indicate that IgM and IgA RF are present in a significant minority of JRA patients and suggest that there is independent expression of the respective RF isotypes.     

Comparative study of different enzyme immunoassays for measurement of IgM and IgA rheumatoid factors

OBJECTIVE: To compare the value of various IgM and IgA rheumatoid factor (RF) tests for the diagnosis of rheumatoid arthritis (RA). METHODS: Firstly, the latex test, one global assay (for IgM, IgA, and IgG RF), six IgM, and four IgA RF assays were compared in a particularly challenging situation-that is, with 67 patients with RA, many of whom were latex negative, and 91 non-RA controls, many of whom were latex positive. More detailed evaluation followed with three IgM RF tests (two commercially available kits and one assay developed in our laboratory) and two IgA RF tests (one commercially available and one from our laboratory) in two more representative samples of rheumatological patients (146 RA and 75 non-RA controls). RESULTS: Diagnostic performance differed considerably between the assays. For IgM RF detection the highest sensitivity (88%) was obtained with the Diamedix kit (specificity 67%) and for IgA RF with the Inova kit (sensitivity 65%, specificity 88%). Combining one IgM and one IgA RF test improved diagnostic performance when both tests were in agreement, but at the cost of yielding 15-27% of discrepant results which did not help in ruling RA in or out. Mean concentration values differed significantly among IgM RF tests, and in most cases concentrations were not correlated. CONCLUSIONS: Available tests for IgM RF isotype vary in accuracy, and none is uniformly better than all the others. For IgA RF isotype, the Inova kit appears to be the best. Quantitative results cannot be compared across tests. Combination of one IgM and one IgA RF test may improve diagnostic accuracy.     

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.     

Class-specific rheumatoid factors, DR antigens, and amyloidosis in patients with rheumatoid arthritis.

Class-specific rheumatoid factors (RFs) were measured by enzyme immunoassay in 59 patients with rheumatoid arthritis complicated by systemic amyloidosis (RA+A), 47 patients with rheumatoid arthritis without amyloid (RA), 106 patients with other rheumatic diseases (juvenile rheumatoid arthritis, systemic lupus erythematosus, Sjögren''s syndrome), and 55 blood donors. The patients with RA+A were characterised by a high prevalence of RF negativity; the IgM RF concentration was raised in only 18 of the 59 patients (31%, p less than 0.001 v RA), the IgG RF concentration in 20 of 59 (34%, p less than 0.001 v RA), and the IgA RF concentration in 24 of 59 (41%, p less than 0.001 v RA). A higher prevalence of HLA-DR4 (p less than 0.001) and a lower prevalence of DR2 (p less than 0.05) were found among 48 tested patients with RA+A when compared with a control panel consisting of 500 blood donors. No significant differences in the prevalence of DR1-DR7 or B27 antigens were observed, however, between patients with RA with or without amyloid.     

Smoking, lung function, and rheumatoid factors.

Positive rheumatoid factor (RF) reactions commonly precede the onset of clinically manifest rheumatoid arthritis (RA). Thus if items associated with RF reactions were traced at the community level this might provide clues to the cause of RA. The relations between smoking and lung functions and the occurrence of RA and RFs in a population sample representative of the adult Finnish population were studied. Rheumatoid factor testing was performed for 7124 subjects (89% of the sample) by the sensitised sheep cell agglutination test. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were measured with spirometry. 'False positive' RF reactions occurred twice as often in current smokers and ex-smokers than in those who had never smoked. The prevalence of high titres was fourfold greater among current smokers than among those who had never smoked. These associations were statistically significant and independent of age, FVC, and FEV1 in both sexes. The women with airflow limitation (FEV1/FVC less than 70%) had a significantly increased occurrence of RFs which was independent of their smoking history, but no such relationship was found in men. The results suggest an impact of smoking on RF production; a follow up study may show whether the raised RF titers in smokers will be reflected as an increased incidence of RA.     

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)     

The prevalence of rheumatoid factor isotypes and anti-cyclic citrullinated peptides in Malaysian rheumatoid arthritis patients

Aim: The purpose of this study is to compare the prevalence of rheumatoid factor (RF) isotypes and second generation anti‐cyclic citrullinated peptides (anti‐CCP) in Malaysian rheumatoid arthritis (RA) patients. Methods: In this cross‐sectional study, 147 established RA patients from three ethnic groups were recruited from a major rheumatology clinic in Malaysia. Enzyme‐linked immunosorbent assays (ELISA) for serum RF isotypes IgA, IgG and IgM as well as second‐generation anti‐CCP were performed and the prevalence of each auto‐antibody was compared in the three ethnic groups. Results: The anti‐CCP was the most prevalent auto‐antibody in each of the ethnic groups, followed closely by RF IgM and RF IgG. Rheumatoid factor IgA was the least prevalent across all three ethnic groups. The anti‐CCP–RF IgM combination provided the best test sensitivity. Seroprevalence of anti‐CCP was strongly associated with the presence of each of the RF isotypes. The seroprevalence of RF and anti‐CCP did not increase or decrease with advancing age, age at onset and disease duration. Conclusion: When used alone, anti‐CCP provides a diagnostic advantage over RF IgM on the basis of test sensitivity. Considering the high cost of the anti‐CCP assay, step‐wise serum testing with IgM RF followed by anti‐CCP may provide a more economically sensible option to optimize test sensitivity for RA.     

Anti-cyclic citrullinated peptide antibody isotypes in rheumatoid arthritis: association with disease duration, rheumatoid factor production and the presence of shared epitope

OBJECTIVE: Anti-cyclic citrullinated peptide (anti-CCP) antibodies of IgG isotype are specific diagnostic markers of rheumatoid arthritis (RA). Recent evidence also points to their direct involvement in the pathophysiology. Little information is available, however, regarding the isotype distribution of anti-CCP antibodies and the characteristics of IgA and IgM anti-CCP. METHODS: IgG, IgA and IgM anti-CCP2 and rheumatoid factor (RF) levels were measured in the sera of 119 RA patients and 118 controls, including patients with other rheumatic diseases and healthy subjects. We analyzed the diagnostic performance of IgA and IgM anti-CCP2 antibodies and their relationship with IgG anti-CCP2, RFs, disease duration and the presence of HLA-DRB1 shared epitope (SE) alleles. RESULTS: Patients with RA had significantly higher serum IgA and IgM anti-CCP2 antibody levels than healthy subjects and patients with other rheumatic diseases (p<0.0001). IgG, IgA and IgM anti-CCP2 antibodies were present in 74.8%, 52.9% and 44.5% of RA patients, and their diagnostic specificity was 95.8%, 95.8% and 91.6%, respectively. The presence of anti-CCP2 antibodies was significantly associated with SE alleles (p=0.03). The frequency of IgM anti-CCP2 positivity was lower in longstanding disease compared to early RA (p=0.03). CONCLUSION: IgA and IgM anti-CCP2 antibodies are present in RA patients, and they are similarly specific for RA as IgG anti-CCP2. The higher frequency of IgM anti-CCP2 antibodies in early RA suggests that they are mostly generated during the first phase of immune response; nonetheless, their production seems to be sustained in some patients. Further analysis of IgM and IgA anti-CCP2 antibodies may provide insights into the pathogenesis of RA.     

Diagnostic and clinical value of anti-cyclic citrullinated peptide antibodies compared with rheumatoid factor isotypes in rheumatoid arthritis

OBJECTIVE: To assess the additional diagnostic and clinical value of the second test generation of anti-cyclic citrullinated peptide antibodies (CCP2) compared with rheumatoid factor isotypes (IgG-RF, IgA-RF, IgM-RF) in patients with rheumatoid arthritis. METHODS: This was a prospective study on 715 patients: rheumatoid arthritis (n = 295), degenerative or other inflammatory joint disease (n = 163), connective tissue disease or vasculitis (n = 103), and healthy controls (n = 154). Sera from each subject were tested for CCP2 and RF isotypes by enzyme linked immunosorbent assay (ELISA). Agreement with clinical indices such as disease activity, joint destruction, disease duration, and other laboratory tests was assessed. Sensitivity and specificity of the tests were evaluated taking the clinical diagnosis as the gold standard. RESULTS: Highest sensitivity was found for IgM-RF (66.4%) and CCP (64.4%). Highest specificity was achieved by CCP (97.1%) and IgG-RF (91.0%). In rheumatoid patients with high disease activity or severe joint damage, CCP was more often present (81.4% and 83.6%) than all RF isotypes. Of special diagnostic value was the detection of positive CCP in 34.5% of all patients with rheumatoid arthritis when all measured RF isotypes (IgG-RF, IgA-RF, and IgM-RF) were negative. CONCLUSIONS: As a screening method for rheumatoid arthritis the IgM-RF and the CCP assays are superior to other RF isotypes. Positivity in the highly specific CCP ELISA supports the diagnosis of rheumatoid arthritis. CCP proved to be a powerful diagnostic tool, especially in ambiguous cases or RF negative patients with rheumatoid arthritis.     

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.