Background:The relationship between the pathological findings and disease relapse has not been well established.Objectives:We aim to investigate the clinical and pathological manifestations in relation with disease relapse in IgG4-RD, as well as identify prognostic factors in predicting relapsed disease.Methods:This study enrolled 71 patients newly diagnosed with IgG4-RD between Jan 2011 and April 2020, all of whom had received pathological examinations. Their pathological manifestations and clinical data were collected. Multivariate Cox regression and AUC (area under curve) were used to identify predictors for relapsed disease and assess the predictive value of these predictors, respectively.Results:During a follow-up period of 26 (range, 6-123) months, 4.2% (3/71) patients died. The remaining 68 patients were all treated with glucocorticoids with or without immunosuppressor continuously. By the end of follow-up, 47 (69.1%) patients sustained clinical remission, and 21 (30.9%) patients suffered relapsed disease with a median relapse time at 10 (6-30) months. We found that IgG4 ≥ 6.5g/L (OR 1.52-11.06), IgG ≥ 20.8g/L (OR 1.11-7.23), IgG4-RD responder index (RI) ≥ 9 (OR 1.28-11.37), and more IgG4+ plasma cell infiltration (≥ 60 / HPF in visceral organs, or ≥ 200 / HPF in head and neck organs) (OR 1.79-22.41) were all independent predictive factors for disease relapse. A prognostic score was explored for predicting recurrence in IgG4-RD, including three predictive factors (IgG ≥ 20.8g/L, IgG4-RD RI ≥9, and more IgG4+ plasma cell infiltration). The three-year relapse rate for the patients with no, one, two, and three risk factors were 0%, 27.3%, 66.7%, and 100%, respectively.Conclusion:Patients’ earlier IgG4 ≥ 6.5g/L, IgG ≥ 20.8g/L, IgG4-RD RI ≥9, and more IgG4+ plasma cell infiltration independently predicted disease relapse. We explored a prognostic score for predicting recurrence in IgG4-RD include three predictive factors (IgG ≥ 20.8g/L, IgG4-RD RI ≥9, and more IgG4+ plasma cell infiltration), which might be used to evaluate the risk of recurrence in IgG4-RD.References:[1]DESHPANDE V, ZEN Y, CHAN J K, et al. Consensus statement on the pathology of IgG4-related disease[J]. Mod Pathol,2012,25(9): 1181-1192.[2]JENNETTE J C, FALK R J, BACON P A, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides[J]. Arthritis Rheum,2013,65(1): 1-11.[3]OKAZAKI K, UMEHARA H. Are Classification Criteria for IgG4-RD Now Possible? The Concept of IgG4-Related Disease and Proposal of Comprehensive Diagnostic Criteria in Japan[J]. Int J Rheumatol,2012,2012: 357071.[4]SHIMOSEGAWA T, CHARI S T, FRULLONI L, et al. International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the International Association of Pancreatology[J]. Pancreas,2011,40(3): 352-358.[5]OHARA H, OKAZAKI K, TSUBOUCHI H, et al. Clinical diagnostic criteria of IgG4-related sclerosing cholangitis 2012[J]. J Hepatobiliary Pancreat Sci,2012,19(5): 536-542.[6]KAWANO M, SAEKI T, NAKASHIMA H, et al. Proposal for diagnostic criteria for IgG4-related kidney disease[J]. Clin Exp Nephrol,2011,15(5): 615-626.[7]GOTO H, TAKAHIRA M, AZUMI A. Diagnostic criteria for IgG4-related ophthalmic disease[J]. Jpn J Ophthalmol,2015,59(1): 1-7.[8]MATSUI S, YAMAMOTO H, MINAMOTO S, et al. Proposed diagnostic criteria for IgG4-related respiratory disease[J]. Respir Investig,2016,54(2): 130-132.[9]WEN ZHANG J H S. Management of IgG4-related disease[J]. Lancet Rheumatol,2019,1: e55-e65.[10]EBBO M, DANIEL L, PAVIC M, et al. IgG4-related systemic disease: features and treatment response in a French cohort: results of a multicenter registry[J]. Medicine (Baltimore),2012,91(1): 49-56.Disclosure of Interests:None declared
IgG4-Related Disease without Overexpression of IgG4: Pathogenesis Implications