Sjögren Syndrome and Cryoglobulinemic Glomerulonephritis

Abstract

We report the case of a 53-year-old woman with Sjögren syndrome and cryoglobulinemia. The patient presented with nephrotic syndrome, hematuria, and reduced estimated glomerular filtration rate. The kidney biopsy revealed diffuse endocapillary proliferation and leukocyte exudation with focal intraluminal hyaline thrombi, prominent tubulointerstitial inflammation, and vasculitis. Diffuse granular mesangial and segmental to global capillary wall staining was observed on immunofluorescence with antisera to C3 and immunoglobulin M (IgM), with less intense staining indicative of IgG and κ and λ light chains. A biopsy diagnosis of Sjögren syndrome-related cryoglobulinemic membranoproliferative glomerulonephritis and vasculitis was rendered. Subsequent investigations revealed the presence of circulating type II cryoglobulins with cryocrit of 9%. Although rare, Sjögren syndrome is the most common cause of non-hepatitis C virus-related mixed cryoglobulinemia. We discuss the possible pathogenic mechanisms involved in the development of mixed cryoglobulinemia and its evolution to lymphoma, as best described in the setting of hepatitis C virus infection. Although the specific antigen involved is unknown, it is likely that the mixed cryoglobulinemia in Sjögren syndrome is triggered by the long-term B-cell stimulation, resulting in clonal proliferation of B cells. Additional chromosomal aberrations and cytokine milieu alterations, as seen in hepatitis C virus infection, may result in prolonged B-cell survival and progression to non-Hodgkin lymphoma.

Clinical and morphologic spectrum of renal involvement in patients with HBV‐associated cryoglobulinaemia

“…Cryoglobulins are synthesized by monoclonal B cells in type I and by polyclonal B cells in type III cryoglobulinaemia. Type II mixed cryoglobulinaemia represents an evolution from a polyclonal B‐cell population to an oligoclonal B‐cell expansion in the setting of long‐term antigenic stimulation and is considered to be a transition phase between autoimmunity and neoplasia . HBV may produce cryoglobulinaemia in a similar way to HCV.…”

“…Type II mixed cryoglobulinaemia represents an evolution from a polyclonal B-cell population to an oligoclonal B-cell expansion in the setting of long-term antigenic stimulation and is considered to be a transition phase between autoimmunity and neoplasia. 18 HBV may produce cryoglobulinaemia in a similar way to HCV. However, it is not yet clear why HBV induces the production of MC in some patients but not in others.…”

Procaine stimulates aquaporin‑5 expression in human salivary gland ductal cells via the suppression of DNA methyltransferase‑1

“…Sjogren's syndrome (SS) is a chronic inflammatory autoimmune disease that usually results from a functional decline caused by lymphocyte invasion into salivary and lacrimal glands, and is associated with a dry mouth, dry eyes and other symptoms (1,2). In the United States, SS has been listed as the second most common human autoimmune disease (3). Worldwide, >80% of patients with SS suffer from oral dryness, diminished taste, angular cheilitis and oral bacterial infections (4).…”

A patient presenting with isolated hematuria and renal dysfunction as rare manifestation of cryoglobulinemic glomerulonephritis in the course of autoimmune diseases including Sjögren’s syndrome

“…In addition, 35% of patients with thyroid disorder showed sicca features, which makes it difficult to determine whether our patient is primary SS or secondary SS associated with autoimmune thyroiditis [9]. Although cryoglobulin typing could not be determined in our case, the depositions of C3 along with IgM and IgG in the glomerular capillary walls and the subendothelial deposits with tubular structures indicated the immune complex formation and presence of mixed cryoglobulinemia [3]. It is possible that staining of strongly positive κ and weakly positive λ in our patient explains type II cryoglobulinemia containing monoclonal IgM and polyclonal IgG.…”

“…Renal manifestations of non-HCV-related CG are variable and its typical renal manifestation includes high amount of proteinuria with microscopic hematuria and renal insufficiency [1,2]. Most kidney specimens of CG showed membranoproliferative glomerulonephritis (MPGN) with subendothelial deposits with or without organized structures [1,3].…”