The Coexistence of Sjögren's Syndrome and Primary Biliary Cirrhosis: A Comprehensive Review

Abstract

Organ-specific and systemic autoimmune diseases share numerous features and often coexist in the same patient. Autoimmune cholangitis/primary biliary cirrhosis and Sjogren syndrome represent paradigmatic examples of the common grounds of different autoimmunity phenotypes based on similarities in clinical manifestations and immunopathogenesis. In fact, primary biliary cirrhosis and Sjogren's syndrome have both been coined as an autoimmune epithelitis in which apoptosis may be in both cases the key element to explain the organ-specific immune-mediated injury against the biliary and exocrine gland epithelia, respectively. Further, growing evidence supports in both diseases the view that B cells, T cytotoxic cells, and T helper cells are involved in chronic inflammation, likely via the altered expression of pro-inflammatory cytokines. The presence of estrogen receptors on the biliary and exocrine gland epithelia has been advocated as a key to the female predominance encountered in primary biliary cirrhosis and Sjogren's syndrome. Sadly, despite available data, therapeutic approaches remain largely unsatisfactory and recent studies with mechanistic approaches (as in the case of B cell depletion with rituximab) have been of partial benefit only. Future studies should focus on new molecular tools (single-cell transcriptomics, microRNA, epigenetics) to provide unique insights into common mechanisms.

Tissue‐Resident Memory CD8+ T Cells Acting as Mediators of Salivary Gland Damage in a Murine Model of Sjögren's Syndrome

“…SS is similar to primary biliary cholangitis in that activated infiltrating T cells can cause severe damage in epithelial structures; therefore, both diseases are considered to be an autoimmune epithelitis with overlapping features (). In the present study, we observed that p40 −/− CD25 −/− mice exhibiting severe autoimmune cholangitis, including hepatic fibrosis (), also recapitulated key features of human SS.…”

The Natural History and Prognosis of Primary Biliary Cirrhosis with Clinical Features of Autoimmune Hepatitis

“…There have been extraordinary and extensive studies of the genetic basis, the immunological features, and the molecular characteristics of not only human PBC but also of several mouse models [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21].…”

Primary rectal mucosa-associated lymphoid tissue lymphoma in a patient with previously identified primary biliary cirrhosis and secondary Sjögren’s syndrome

“…The patient, who was being followed for previously identified PBC and SjS, developed primary rectal MALT lymphoma with gastric mucosal atrophy on upper gastrointestinal endoscopy, but no H. pylori infection. SjS-associated malignant lymphoma is thought to result when chronic inflammation from autoimmunity causes T lymphocytes to release cytokines that cause B-lymphocyte proliferation and monoclonal transformation [ 14 ]. The resulting B-cell hyperplasia is thought to progress to MALT lymphoma over many years, and become highly malignant.…”