Anti-centromere antibody positivity with coexisting idiopathic portal hypertension and primary biliary cholangitis progressing to limited cutaneous systemic sclerosis: a case report.

Background: Anti-centromere antibodies are autoantibodies that selectively bind to the centromere region of chromosomes. Studies have indicated that anti-centromere antibodies can induce microvascular alterations and tissue remodeling, ultimately leading to fibrosis. They have been implicated in limited cutaneous systemic sclerosis, including calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia syndrome, and primary biliary cholangitis, where anti-centromere antibody positivity can be associated with rapid progression of portal hypertension, although the underlying mechanisms remain unclear. Idiopathic portal hypertension, despite being termed "idiopathic," has distinctive pathological, angiographic, and ultrasound findings, and autoimmune processes have been proposed to mediate its intrahepatic microcirculatory disruptions. Interestingly, idiopathic portal hypertension-related small portal vein and scleroderma skin findings share certain similarities. However, no documented cases have linked anti-centromere antibody-induced intrahepatic vascular endothelial dysfunction to idiopathic portal hypertension and subsequent progression to limited cutaneous systemic sclerosis.

Case presentation: A 57-year-old Japanese woman was referred to our hospital with suspected anti-centromere antibody-positive primary biliary cholangitis. Further examination revealed the coexistence of idiopathic portal hypertension, and the patient progressed to limited cutaneous systemic sclerosis over 3 years. On the basis of this case, we suspected that anti-centromere antibodies might cause microvascular endothelial dysfunction, leading to the development of idiopathic portal hypertension and other systemic abnormalities. Supplementary tests were performed to verify this hypothesis, including flow-mediated vasodilation, brachial-ankle pulse wave velocity, nailfold video capillaroscopy, upper gastrointestinal endoscopy, pathological CD34 and indoleamine 2,3-dioxygenase 1 staining, and measurements of soluble lectin-like oxidized low-density lipoprotein receptor-1 and its ligand containing apolipoprotein B. The results indicated vascular abnormalities in the liver, skin, and gastrointestinal tract, highlighting the universal effects of anti-centromere antibodies in vascular and autoimmune pathologies.

Conclusion: This is the first documented case of hepatic and systemic microvascular impairment observed in an anti-centromere antibody-positive patient. The pathological evidence of endothelial damage in the liver suggests that the "idiopathic" label of idiopathic portal hypertension may need reconsideration in the context of anti-centromere antibody-related pathophysiology, potentially warranting a unifying concept such as "anti-centromere antibody-related systemic microangiopathy syndrome." While our case may provide novel insights into anti-centromere antibody-driven microvascular dysfunction across multiple organ systems, the findings are preliminary. Future studies involving larger cohorts and detailed mechanistic analyses are necessary to confirm the systemic and hepatic effects of anti-centromere antibodies.