Rheumatoid Factor Positivity in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

A Distinct Clinical Entity or Innocent Bystander?

Sung Soo Ahn; Jang Woo Ha; Yong-Beom Park; Sang-Won Lee


Rheumatology. 2022;61(4):1366-1375. 

In This Article

Abstract and Introduction


Objective: To investigate the significance of RF positivity in ANCA-associated vasculitis (AAV) patients.

Methods: AAV patients were divided into groups as follows: RF (+)/ANCA (+) (n = 94), RF (−)/ANCA (+) (n = 80), RF (+)/ANCA (−) (n = 15) and RF (−)/ANCA (−) (n = 25). Their clinical data, organ involvement patterns, laboratory data, and patient outcomes were assessed. Kaplan–Meier analysis and propensity score matching (PSM) were performed to compare outcomes and analyse differences between the groups.

Results: Of the 214 patients, RF and ANCA positivity was found in 109 (50.9%) and 174 (81.3%) patients, respectively. RF (+)/ANCA (+) patients more frequently presented with general manifestations (58.5%) than the other groups. Additionally, compared with those of RF (−)/ANCA (+) group, RF (+)/ANCA (+) patients were older, had higher white blood cell, neutrophil, platelet counts and acute phase reactants; however, creatinine and albumin levels were lower. The end-stage kidney disease-free survival rate was significantly higher in the RF (+)/ANCA (+) group (P =0.013), while the proportion of renal involvement was comparable to the RF (−)/ANCA (+) group. PSM showed no difference in patient outcomes between the two groups after adjustment.

Conclusion: RF positivity was associated with a distinct phenotype in AAV patients. In particular, difference was observed in clinical features and outcomes between RF (+)/ANCA (+) and RF (−)/ANCA (+) groups, although the direct prognostic implication of RF was not evident.


Primary systemic vasculitides (PSV) refer to a group of chronic autoimmune disorders affecting various-sized vessels.[1,2] Among the primary systemic vasculitides, ANCA-associated vasculitis (AAV) is characterized by necrotizing inflammation of the small- and medium-sized vessels, which is typically associated with the production of ANCAs against MPO or proteinase 3 (PR3). A traditional approach of categorizing AAV is to classify it into three different subgroups clinically according to the patterns of affected organs and the types of ANCAs detected: microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (EGPA).[3] However, the features of AAV are largely variable and substantial genetic and geographic disparities exist; therefore, continuous efforts have been made to better define the subtypes of AAV patients.[4] Recently, accumulating evidence has suggested that categorizing AAV patients based on ANCA specificity could aid in identifying patients with similar characteristics.[5] This method of classification is significant because it could provide more information on treatment response, disease relapse and long-term outcomes that are relevant to patient prognosis.[6,7] Nevertheless, owing to the diverse clinical spectrum of AAV in patients, a better understanding of this complex, heterogeneous disorder is necessary.

RF, a classic autoantibody that was initially identified in patients with RA, is widely tested in clinical practice for differentiating between the causes of joint pain.[8] However, considering that RF is detected in cases of several rheumatic and non-rheumatic diseases as well as in healthy subjects, its accuracy in diagnosing RA is restricted when clinical features suggestive of inflammatory arthritis are absent.[9] Further, there are reports suggesting that RF is also frequently found in the peripheral circulation of patients with systemic vasculitis.[10] Similarly, we have previously found that RF was present in ~40% of patients with AAV, although the effect that RF had on the risk of relapse was unclear.[11] We have also demonstrated that RF positivity was associated with cutaneous manifestation in EGPA patients at the time of diagnosis, suggesting that this antibody could have clinical relevance in AAV and should be further investigated. Therefore, in this study, we aimed to evaluate whether patients with AAV possessing RF had distinct clinical features and different outcomes.