Background/Purpose:

Connective tissue diseases (CTDs) are characterised by specific autoantibodies which are useful for diagnosis. Rare antibodies have been described in CTDs in several case series. We assessed the frequency and clinical features of CTD patients attending our centre, positive for at least one of these antibodies (Jo-1, PCNA, XR, PL-4, PL-7, PL-12, SRP, Ku, Mi-2, EJ, SL, PmScl, rRNP, Th/To, NuMa-1, OJ and hnRNP). Rare antibody was defined as an antibody found in less than 5% of our patient population.

Methods:

The immunology results for 5828 patients obtained over the past 17 years were analysed and patients with the rare antibodies were identified. Clinical data including diagnosis and frequency of organ involvement were obtained from medical records and patient review.

Results:

758 patients (12.5%) were positive for at least one rare antibodies. Clinical information confirming a diagnosis of a CTD was available for 514 patients. The most common rare antibody was PmScl (3.1%) and least common was OJ (0.01%). The majority of patients with rare autoantibodies demonstrated overlap syndromes (32.1%), the second most common diagnosis was scleroderma (SSc) (31.0%). The least common diagnosis was UCTD (1.1%).

Further analyses of major organ involvement by antibody subtype revealed 82.4% of PL-7+ patients had interstitial lung disease (ILD). ILD was also frequently seen in PL12+ (75%), Jo-1+ (70.8%), SRP+ patients (66.7%) and Mi-2 (57%). PCNA, NuMa1, OJ and hnRNP were not associated with ILD. Pulmonary arterial hypertension (PAH) was most frequently seen in XR+ patients (31.8%), followed by Th/To+ (25%) and Jo-1 (15.3%) patients. None of our patients with PL-12 developed PAH. Inflammatory myositis (IM) was found in all Jo1+ and SRP+ patients, and in the majority of PL-7+ (88.2%) patients. Inflammatory arthritis was more commonly seen in hnRNP+ (100%), PCNA+ (57.1%), SL+ (38.3%), and PL-12+ (33.3%) patients but not reported in EJ+, Mi-2+ and PL-4+ patients. Glomerulonephritis was reported in significant proportion of rRNP+ (60%), PCNA+ (42.9%), and PL-4+ (45.5%) patients. Scleroderma renal crisis was diagnosed in three (3.8%) SL+ patients.

Conclusion:

Our data from a large cohort of patients with CTDs suggest that rare antibodies associate with characteristic features, in particular ILD and inflammatory myositis. A majority of these patients fulfil the criteria for overlap syndrome and SSc.

We noted some associations not reported in current literature between these antibodies and fibrotic and vascular features of CTDs. In contrast to previous findings, ILD was frequently reported in our Mi-2+ patients. Anti XR has not previously been associated with PAH or ILD, whereas we noted a frequency of 31.8% and 40.9% respectively.

Given the rarity of these antibodies, it is important to understand the clinical impact they may have in risk stratifying our patients at diagnosis especially given the high proportion of patients with overlap CTD features.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/frequency-and-clinical-associations-of-rare-antibodies-in-a-large-connective-tissue-disease-cohort/