Anti-Ku antibody syndrome: is it a distinct clinical entity? A cross-sectional study of 75 patients

Sousa, Marlene; Martins, Patrícia; Santos, B.; Costa, Emanuel; Santos, Filipe Cunha; Freitas, Raquel; Faria, Margarida; Martins, F. R.; Rodrigues, Teresa; Santiago, Tânia; Silva, José A P; Inês, Luís

doi:10.1093/rheumatology/kead049

Cited by 8 publications

(3 citation statements)

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“…Most of the patients had isolated myositis or overlap with systemic sclerosis (30.8% respectively), whereas overlap with SLE and Sjögren’s syndrome was present in 11.5%. It is known that the presence of Ku-antibodies is not necessarily associated with myositis but can also occur in healthy individuals or with other organ involvement than myositis [ 64 ]. Interestingly, there seem to be regional differences, as in the United States, Ku-antibodies are found in SLE, whereas, in Japan, they are often associated with myositis or systemic sclerosis [ 17 , 48 ].…”

Section: Discussionmentioning

confidence: 99%

Anti-Ku + myositis: an acquired inflammatory protein-aggregate myopathy

Holzer,

Uruha,

Roos

et al. 2024

Acta Neuropathol

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Myositis with anti-Ku-autoantibodies is a rare inflammatory myopathy associated with various connective tissue diseases. Histopathological studies have identified inflammatory and necrotizing aspects, but a precise morphological analysis and pathomechanistic disease model are lacking. We therefore aimed to carry out an in-depth morpho-molecular analysis to uncover possible pathomechanisms. Muscle biopsy specimens from 26 patients with anti-Ku-antibodies and unequivocal myositis were analyzed by immunohistochemistry, immunofluorescence, transcriptomics, and proteomics and compared to biopsy specimens of non-disease controls, immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM). Clinical findings and laboratory parameters were evaluated retrospectively and correlated with morphological and molecular features. Patients were mainly female (92%) with a median age of 56.5 years. Isolated myositis and overlap with systemic sclerosis were reported in 31%, respectively. Isolated myositis presented with higher creatine kinase levels and cardiac involvement (83%), whereas systemic sclerosis-overlap patients often had interstitial lung disease (57%). Histopathology showed a wide spectrum from mild to pronounced myositis with diffuse sarcolemmal MHC-class I (100%) and -II (69%) immunoreactivity, myofiber necrosis (88%), endomysial inflammation (85%), thickened capillaries (84%), and vacuoles (60%). Conspicuous sarcoplasmic protein aggregates were p62, BAG3, myotilin, or immunoproteasomal beta5i-positive. Proteomic and transcriptomic analysis identified prominent up-regulation of autophagy, proteasome, and hnRNP-related cell stress. To conclude, Ku + myositis is morphologically characterized by myofiber necrosis, MHC-class I and II positivity, variable endomysial inflammation, and distinct protein aggregation varying from IBM and IMNM, and it can be placed in the spectrum of scleromyositis and overlap myositis. It features characteristic sarcoplasmic protein aggregation on an acquired basis being functionally associated with altered chaperone, proteasome, and autophagy function indicating that Ku + myositis exhibit aspects of an acquired inflammatory protein-aggregate myopathy.

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Section: Discussionmentioning

confidence: 99%

Anti-Ku + myositis: an acquired inflammatory protein-aggregate myopathy

Holzer,

Uruha,

Roos

et al. 2024

Acta Neuropathol

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show abstract

“…1 Recently, a subset of patients with isolated positivity for anti-Ku antibodies (anti-Ku syndrome) presenting with Raynaud's phenomenon, arthritis and sicca syndrome has been described. 2 Categorization of patients with anti-Ku syndrome is challenging due to the lack of classification criteria and scarce information published to date.…”

Section: Anti-ku Syndrome: a Novel Cause Of Fever Arthritis And Rashmentioning

confidence: 99%

“…Sousa et al 2 have reported a group of patients who test positive only for anti-Ku antibodies and predominantly presented with Raynaud's phenomenon, arthritis and sicca syndrome. Our patient presented with similar symptoms along with intermittent fever and dermatosis.…”

Section: E243mentioning

confidence: 99%