TAP-I Deficiency Presenting With Chronic Granulomatous Rubella Virus-Driven Cutaneous Ulceration - A Case Report and Scoping Literature Review

Sep 30, 2026

Uploaded by Eliana

Autosomal recessive mutations in TAP1, TAP2, TAPBP, or B2M cause major histocompatibility complex (MHC) class I deficiency, which can present with granulomatous skin ulceration despite unclear antigenic triggers. A 32-year-old woman with 7 years of localized ulcers was found to have TAP1 deficiency. Rubella virus infection was identified as a likely inflammation driver, and topical calcineurin inhibition provided modest improvement. A scoping review identified 45 individuals across 36 reports with 1,184 patient-years of follow-up, highlighting chronic necrotizing granulomatous lesions, bronchiectasis, diagnostic delay, and respiratory-related deaths.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Abstract

Introduction

Methods

Flow Cytometry

Whole-Exome Sequencing

Rubella Detection

Journal of Clinical Immunology (2026) 46:1 [https://doi.org/10.1007/s10875-025-01919-6](https://doi.org/10.1007/s10875-025-01919-6) RESEARCH TAP-I Deficiency Presenting With Chronic Granulomatous Rubella Virus-Driven Cutaneous Ulceration: A Case Report and Scoping Literature Review Mark J. Ponsford1,2,3 · Emily M. Carne1,2 · Kathryn Bramhall2 · Kristin Ladell3 · Ludmila Perelygina4 · Aung Saw1 · Kelly Miners3 · Sian Llewellyn-Lacey3 · Simon Kollnberger3 · Ian Tully1,5 · Sian Hughes6 · Hywel Williams1,7 · Manju Kalavala8 · Venetia Bigley9,10 · Daniel Farewell11 · David A. Price3,12 · Stephen L. Walker13,14,15 · Kathleen E. Sullivan16 · Stephen Jolles1,2 · On behalf of the All Wales Syndrome Without A Name (SWAN) Clinic Received: 24 September 2024 / Accepted: 15 July 2025 © The Author(s) 2025 Abstract Autosomal recessive mutations in TAP1, TAP2, TAPBP, or B2M, are associated with major histocompatibility complex (MHC) class I deficiency. Individuals may present with granulomatous skin ulceration, but the underlying antigenic triggers remain largely unknown. We identified TAP1 deficiency in a 32-year-old female referred with a 7-year history of localized skin ulceration. Histologic immunofluorescence revealed that rubella virus (RuV) infection was a likely driver of the associated inflammation, and modest clinical improvement was observed following topical calcineurin inhibition. To better define the natural history, clinical, and immunological manifestations of this condition, we also performed a scoping literature review. We identified 45 unique individuals from 36 reports with a combined follow-up duration of 1,184 patient years. Chronic necrotizing granulomatous skin lesions and childhood-onset bronchiectasis were common. Five deaths were reported (median age 36 years), typically linked to respiratory complications. Phenotypic heterogeneity was evident, with at least four individuals reaching adulthood without clinical symptoms. Diagnostic delay frequently exceeded a decade amongst symptomatic individuals, with misdiagnosis of granulomatous disease prompting systemic immunosuppression and infection-related morbidity. The presence of an abnormal CD8+ T-cell count or a history of consanguinity offered low sensitivity for MHC I deficiency (~ 50%), indicating a low threshold for further investigation is required for correct diagnosis. Graphical review of case reports identified morphologically similar lesions in other MHC I-deficient individuals. These findings suggest that the phenomenon of MHC I deficiency is underreported and that diagnosis should prompt testing for RuV. Keywords TAP1 · MHC 1 · Immunodeficiency · Rubella Introduction Individuals with inborn errors of immunity often present following diagnostic delay, which can result in substantial morbidity and healthcare costs [1] . Skin manifestations, such as erythroderma, eczematous lesions, or infection, may be present in up to half of these patients at the time of primary immunodeficiency diagnosis [2] . The nature and severity of these clinical manifestations should alert clinicians to the possibility of immunodeficiency [3] . Chronic Extended author information available on the last page of the article granulomatous skin lesions can be a presenting feature of major histocompatibility complex (MHC) class I deficiency, a rare autosomal recessive condition caused by mutations in the transporter associated with antigen processing (TAP) [4] . However, the antigenic triggers for the cutaneous granulomas associated with MHC class I deficiency have remained largely elusive. Granulomas associated with rubella virus (RuV) infection have recently been reported in individuals with TAP1 and TAP2 deficiency [5, 6] . Here, we report a case of a TAP1 deficiency diagnosed as a consequence of 1 3 chronic granulomatous skin ulceration and identify RuV infection as the likely causative agent. To inform diagnosis and management of similar individuals, we perform

FAQs

What condition is described in this case report?

The report describes TAP-I deficiency presenting with chronic granulomatous skin ulceration driven by rubella virus infection, along with a review of related cases.

How was rubella virus involved in the patient’s inflammation assessed?

Rubella virus capsid antigen was detected in histological sections, supporting rubella virus as a likely driver of the associated inflammation.

What did the scoping literature review determine about reported patients?

The review identified 45 unique individuals from 36 reports, commonly showing chronic necrotizing granulomatous skin lesions and childhood-onset bronchiectasis, with frequent diagnostic delay and respiratory complications contributing to deaths.

Sep 30, 2026

Uploaded by Eliana