Heterogeneity of autoantibodies in 100 patients with autoimmune myositis: insights into clinical features and outcomes

Abstract

The objective of this study was to determine the prevalence, mutual associations, clinical manifestations, and diagnoses associated with serum autoantibodies, as detected using recently available immunoassays, in patients with autoimmune myositis (AIM). Sera and clinical data were collected from 100 patients with AIM followed longitudinally. Sera were screened cross-sectionally for 21 autoantibodies by multiplex addressable laser bead immunoassay, line blot immunoassay, immunoprecipitation of in vitro translated recombinant protein, protein A assisted immunoprecipitation, and enzyme-linked immunosorbent assay. Diagnoses were determined using the Bohan and Peter classification as well as recently proposed classifications. Relationships between autoantibodies and clinical manifestations were analyzed by multiple logistic regression. One or more autoantibodies encompassing 19 specificities were present in 80% of the patients. The most common autoantibodies were anti-Ro52 (30% of patients), antiKu (23%), anti-synthetases (22%), anti-U1RNP (15%), and antifibrillarin (14%). In the presence of autoantibodies to Ku, synthetases, U1RNP, fibrillarin, PM-Scl, or scleroderma autoantigens, at least one more autoantibody was detected in the majority of sera and at least two more autoantibodies in over one-third of sera. The largest number of concurrent autoantibodies was six autoantibodies. Overall, 44 distinct combinations of autoantibodies were counted. Most autoantibodies were unrestricted to any AIM diagnostic category. Distinct clinical syndromes and therapeutic responses were associated with anti-Jo-1, anti-fibrillarin, anti-U1RNP, antiRo, anti-Ro52, and autoantibodies to scleroderma autoantigens. We conclude that a significant proportion of AIM patients are characterized by complex associations of autoantibodies. Certain myositis autoantibodies are markers for distinct overlap syndromes and predict therapeutic outcomes. The ultimate clinical features, disease course, and response to therapy in a given AIM patient may be linked to the particular set of associated autoantibodies. These results provide a rationale for patient profiling and its application to therapeutics, because it cannot be assumed that the B-cell response is the same even in the majority of patients in a given diagnostic category.

Autoantibodies and microvascular damage are independent predictive factors for the progression of Raynaud's phenomenon to systemic sclerosis: A twenty‐year prospective study of 586 patients, with validation of proposed criteria for early systemic sclerosis

“…Anti-Th/To antibodies were determined in sera displaying a nucleolar pattern of ANA, using protein A-assisted immunoprecipitation for nucleic acid analysis from nonradiolabeled HeLa cells (performed by MK and GB at the University of Sherbrooke) (34). Anti-topo I antibodies were determined by addressable laser bead immunoassay (ALBIA) and ELISA (35)(36)(37). Only sera that showed positive results on both assays were counted as positive.…”

“…Only sera that showed positive results on both assays were counted as positive. For ALBIA, microspheres embedded with laserreactive dyes (Luminex, Austin, TX) coupled with native antigen, which were part of a commercial kit (QuantaPlex SLE Profile 8; Inova Diagnostics, San Diego, CA), were used (performed by MK and MJF at the University of Calgary) (35). Anti-topo I (37) and anti-RNAP III antibodies were detected by ELISA using a kit from MBL (Nagoya, Japan) (performed by MK and J-LS) (35,38).…”

Aminoacyl-tRNA Synthetases in Idiopathic Inflammatory Myopathies: An Update on Immunopathogenic Significance, Clinical and Therapeutic Implications

“…Whereas highly selective, mutually exclusive and associated with particular genotypes with few exceptions, anti-synthetase autoantibodies are strongest associated with the antiwww.intechopen.com synthetase syndrome, a disease subset characterized by a broad clinical spectrum including varying degrees of (i) interstitial lung disease (ILD), (ii) myositis, (iii) non-erosive (poly)arthritis, (iv) fever, (v) Raynaud's phenomenon and (vi) "mechanic's hand" meaning hyperkeratosis with fissuring and hyperpigmentation along the radial and palmar aspects of the fingers (Betteridge et al, 2007;Hirakata, 2005;Mimori et al, 2007;Solomon et al, 2011). More detailed clinical features, investigations and specific management of patients with anti-ARS antibodies have been described in several recent reports Hirakata, 2005;Koenig, 2007;Solomon et al, 2011). Current findings on autoantibodies in anti-synthetase syndrome have already provided important information about clinical phenotypes, course and prognosis related to anti-ARSs status (Lundberg & Grundtman, 2008;Labirua & Lundberg, 2010).…”

The Antisynthetase Syndrome

“…Three years later, the Jo-1 antigen was identified as histidyl-tRNA synthetase (5;6). In recent case series, the anti-Jo-1 antibody accounts for 68-87% of the anti-ARS observed in ASS (7)(8)(9). The seven other anti-ARS identified (Table 1) are all rare, but their relative frequencies have not been extensively studied (7;8).…”