Background/Purpose:

COPA syndrome is a newly discovered primary immunodeficiency resulting in immune dysregulation showing autosomal dominant inheritance with incomplete penetrance. Its name is derived from the mutation of the gene encoding for the alpha subunit of the coatomer complex-I that is responsible for transportation of molecular cargo from the Golgi to the Endoplasmic Reticulum. Previously, studies have elucidated the molecular mechanisms responsible for the disease phenotype. Clinical features of COPA syndrome primarily included pulmonary disease (interstitial lung disease, pulmonary hemorrhage), musculoskeletal (MSK) manifestations, autoantibody formation and renal disease. Here we aim to review and describe the MSK features of this newly defined disorder.

Methods:

After IRB approval, we reviewed the MSK manifestations of patients with COPA mutation, as to characteristic nature, physical findings and diagnostic features. The clinical course of a family from this cohort, that was followed at our institution, was described.

Results:

The previously reported cohort included 21 patients with 62% female. The mean age at presentation was 3.5 years with a range of 6 months to 22 years. Joint pain was present in 24% of patients at initial presentation and joint complaints were mostly intermittent in nature. Findings of arthritis were described in 95% of patients involving both small and large joints along the clinical course, often with polyarticular disease. Most commonly affected joints included the knees, and the interphalangeal joints of the hands. Two patients had osteonecrosis along the femur, patella and tibiofibula. Fatty necrosis was noted in one patient. Notably, presence of autoantibodies was a prominent feature of this disorder: rheumatoid factor (43%), ANA (67%), and ANCA/MPO/PR-3 (71%).

The most common diagnosis included Rheumatoid Arthritis, Juvenile Idiopathic Arthritis and undifferentiated arthritis. Arthralgia exacerbation was found to mirror pulmonary disease flare. Joint manifestation had varying response to NSAID, steroids, methotrexate and anti-TNF therapy. Multimodal anti-inflammatory, immunolytic and immunomodulatory therapy indicated for the severe pulmonary and renal features did not provide prolonged remission of arthritis.

Table 1: COPA patients from single family carrying the R235H mutation

Conclusion:

Musculoskeletal manifestations are a prominent and important feature of COPA syndrome. Due to similarities in clinical features it is difficult to differentiate COPA arthritis from other inflammatory arthropathies of systemic immune mediated disorders.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/musculoskeletal-features-in-copa-syndrome/