IgG4-related disease (IgG4-RD) is a recently recognized fibro-inflammatory disorder that can affect almost any organ. Common presentations include major salivary and lacrimal gland enlargement, orbital disease, autoimmune pancreatitis, retroperitoneal fibrosis and tubulointerstitial nephritis. The main histopathological features are a dense, polyclonal, lymphoplasmacytic infiltrate rich in IgG4+ plasma cells, storiform fibrosis and obliterative phlebitis. The precise pathogenic mechanisms of IgG4-RD are still unclear. CD4+ T and B cells, including IgG4-expressing plasmablasts, constitute the major inflammatory cell populations and are believed to cause organ damage and tissue fibrosis. The diagnosis of the disease may be challenging and should be based on specific histopathological findings, typical laboratory and radiological aspects and an appropriate clinical context. The first-line treatment of IgG4-RD is based on glucocorticoids, which are usually efficacious. However, B cell depletion induced by rituximab has also been found to induce remission in steroid-resistant disease or has been used as steroid-sparing agent for relapsing disease. This review provides an update on clinical and therapeutic aspects of IgG4-RD.

Objective: Chronic periaortitis (CP) is a rare fibro-inflammatory disorder that incorporates idiopathic retroperitoneal fibrosis, inflammatory abdominal aortic aneurysms, and perianeurysmal retroperitoneal fibrosis. CP is included in the spectrum of IgG4-related disease. Since CP patients rarely undergo diagnostic biopsies, serum IgG4 levels are often used to classify CP as IgG4-related. However, the clinical and prognostic significance of serum IgG4 in CP is unknown. Methods: We measured serum IgG4 in active CP patients and compared the clinical characteristics, response to therapy and outcome of patients with high and normal levels. We also tested the diagnostic significance of IgG4 by comparing its levels in CP patients, healthy and disease controls (malignancies, Erdheim-Chester disease, large-, and small-vessel vasculitis). Results: We studied 113 consecutive patients with active CP. Twenty-four (21.2%) had high serum IgG4 (>135 mg/dL). The demographic, laboratory, and clinical characteristics of patients with high and normal IgG4 were similar, and so were the rates of ureteral obstruction and the disease characteristics on CT, MRI, and 18 F-FDG-PET. Patients with high IgG4 only had a higher frequency of extra-retroperitoneal fibro-inflammatory lesions ( p = 0.005). There were no significant differences in response to therapy and relapses between the two groups. Serum IgG4 levels did not discriminate CP from controls. Conclusions: Serum IgG4 levels are high in a minority of CP patients and do not identify specific clinical or prognostic subgroups; only a higher frequency of extra-retroperitoneal lesions is found in high-IgG4 patients. Serum IgG4 levels do not help in the differential diagnosis between CP and its mimics.

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Introduction: In patients with systemic lupus erythematosus (SLE) without concurrent active urinary sediment or unexplained acute kidney injury (AKI), current guidelines recommend performing a kidney biopsy in those with at least 500 mg/24-hour (European League Against Rheumatism/European Renal Association-European Dialysis and Transplant Association [EULAR/ERA-EDTA]) or 1000 mg/24-hour (American College of Rheumatology [ACR]) proteinuria. To evaluate the relevance of these indications, we studied histopathologic findings in patients with SLE with proteinuria below these cutoffs. Methods: We retrospectively reviewed the clinical, laboratory and histological characteristics of patients with SLE with <1000 mg/24-hour proteinuria (or mg/g urinary protein-to-creatinine ratio [UPCR]) who underwent their first kidney biopsy between 2003 and 2018. Results: We identified 87 patients with SLE with proteinuria less than 1000 mg/24-hour (or mg/g UPCR); 52 of 87 (60%) with isolated proteinuria, that is, without AKI or active urinary sediment (hematuria). Histologic evidence of lupus nephritis (LN) was present in 40 of 52 (76%). Of the 40 patients with LN, 12 had class I or II, 14 had class III or IV, 8 had class V, 6 had a combined proliferative and membranous LN. Non-lupus diagnoses included focal segmental glomerulosclerosis, acute interstitial nephritis, and others. Patient's age, low C3, low C4, and positivity for anti-double-stranded DNA (anti-dsDNA) antibodies predicted the histological diagnosis of LN on univariate logistic regression; however, a multivariate model including these parameters as independent covariates failed to predict LN. Conclusions: Patients with SLE with low-level proteinuria may have significant lupus-or non-lupus-related kidney disease with management implications. There was a significant burden of severe forms of LN. The presence of LN was not predicted by laboratory abnormalities. Based on our findings, we suggest current guidelines be revised to expand kidney biopsy indications to include isolated proteinuria of any grade.