To identify similarities and differences in the clinical features of adult Japanese patients with individual anti-aminoacyl-tRNA synthetase antibodies (anti-ARS Abs). This was a retrospective analysis of 166 adult Japanese patients with anti-ARS Abs detected by immunoprecipitation assays. These patients had visited Kanazawa University Hospital or collaborating medical centers from 2003 to 2009. Anti-ARS Ab specificity included anti-Jo-1 (36%), anti-EJ (23%), anti-PL-7 (18%), anti-PL-12 (11%), anti-KS (8%), and anti-OJ (5%). These anti-ARS Abs were mutually exclusive, except for one serum Ab that had both anti-PL-7 and PL-12 reactivity. Myositis was closely associated with anti-Jo-1, anti-EJ, and anti-PL-7, while interstitial lung disease (ILD) was correlated with all 6 anti-ARS Abs. Dermatomyositis (DM)-specific skin manifestations (heliotrope rash and Gottron’s sign) were frequently observed in patients with anti-Jo-1, anti-EJ, anti-PL-7, and anti-PL-12. Therefore, most clinical diagnoses were polymyositis or DM for anti-Jo-1, anti-EJ, and anti-PL-7; clinically amyopathic DM or ILD for anti-PL-12; and ILD for anti-KS and anti-OJ. Patients with anti-Jo-1, anti-EJ, and anti-PL-7 developed myositis later if they had ILD alone at the time of disease onset, and most patients with anti-ARS Abs eventually developed ILD if they did not have ILD at disease onset. Patients with anti-ARS Abs are relatively homogeneous. However, the distribution and timing of myositis, ILD, and rashes differ among patients with individual anti-ARS Abs. Thus, identification of individual anti-ARS Abs is beneficial to define this rather homogeneous subset and to predict clinical outcomes within the “anti-synthetase syndrome.”

Polymyositis (PM) and dermatomyositis (DM) represent a group of chronic inflammatory disorders characterized by myogenic changes, skin eruptions, or both. Clinical features are heterogeneous, with various degrees of skin manifestations, myositis, and pulmonary involvement, which considerably determine the severity and prognosis.¹ Although the causes of these disorders remain unclear, autoimmunity is considered to have a critical role because the presence of diagnostic autoantibodies (Abs), known as myositis-related Abs, is a prominent feature.² A variety of serum Abs are detected in patients with PM/DM, including Abs reactive with aminoacyltransfer RNA synthetase (ARS),³ signal recognition particle,⁴ and Mi-2.⁵ These Abs are associated with clinically distinct subsets of PM/DM, that is, anti-ARS with interstitial lung disease (ILD), arthritis, Raynaud phenomenon, and mechanic hand^6,7; anti–signal recognition particle with acute-onset severe refractory PM^8-10; and anti–Mi-2 with typical DM with a lower risk of ILD and internal malignancy and good response to treatment.^11-13 In addition, anti–PM-Scl, anti-Ku, and anti-U1RNP Abs are associated with myositis overlap syndrome.¹⁴ Therefore, identification of myositis-related Abs is useful in defining clinically homogenous patient subsets, in predicting prognosis, and in clarifying the pathogenesis. Recently, 2 myositis-related Abs, anti–155/140^15,16 and anti–CADM-140,¹⁷ have been reported. Subsequent studies have revealed corresponding autoantigens: transcriptional intermediary factor 1-γ for anti–155/140¹⁸ and melanoma differentiation–associated gene 5 for anti–CADM-140.¹⁹ Anti–155/140 Abs are reported to represent malignancy-associated or juvenile DM,^15,20 and anti–CADM-140 Abs are reported to be associated with amyopathic DM and rapidly progressive ILD (RP-ILD).^17,19 Although precise clinical details of these 2 Abs need to be clarified further, anti–155/140, anti–CADM-140, and anti–Mi-2 Abs are considered to be highly specific for DM.

Objective: To identify the 140‐kd autoantigen recognized by anti‐155/140 autoantibodies that are associated with adult cancer‐associated dermatomyositis (DM) and juvenile DM and to determine the clinical relevance of anti‐155/140 antibodies in a large cohort.Methods: Sera from 456 DM patients were assessed for the presence of anti‐155/140 antibodies by immunoprecipitation using K562 cell extracts as substrate. Using immunoprecipitation and Western blotting, we then examined whether anti‐155/140–positive sera recognized transcription intermediary factor 1α (TIF‐1α), TIF‐1β, and TIF‐1γ. The clinical associations of antigen reactivity were also evaluated.Results: Anti‐155/140–positive sera reacted with 140‐kd TIF‐1α in addition to 155‐kd TIF‐1γ. Among sera from 456 DM patients, 52 were reactive with both TIF‐1α and TIF‐1γ, while another 25 were reactive with TIF‐1γ alone. Additionally, 7 were reactive with TIF‐1β. Malignancy was more frequently found in adult patients with both anti–TIF‐1α and anti–TIF‐1γ antibodies than in those with anti–TIF‐1γ antibodies alone (73% versus 50%; P < 0.05). In addition to juvenile DM patients and middle‐aged and older DM patients with high percentages of malignancy, 8 “young adult” DM patients without malignancy had these autoantibodies.Conclusion: Anti‐155/140 antibodies target TIF‐1 family proteins, TIF‐1α and TIF‐1β, in addition to TIF‐1γ. Since TIF‐1 proteins have significant roles in oncogenesis, these antibodies may be produced during misdirected antitumor immunity.

Objective: To determine serum levels of BAFF, a potent B cell survival factor, in patients with systemic sclerosis (SSc) and relate the results to the clinical features of SSc.Methods: Serum BAFF levels in 83 patients with SSc were examined by enzyme‐linked immunosorbent assay (ELISA). In a longitudinal study, 131 serum samples obtained from 21 patients with SSc were analyzed. The expression of BAFF messenger RNA (mRNA) in the skin was quantified by real‐time reverse transcription–polymerase chain reaction. The expression of BAFF receptor (BAFFR) on CD19+ B cells was assessed by flow cytometry. The production of IgG and interleukin‐6 (IL‐6) by isolated B cells was examined by ELISA.Results: Serum BAFF levels were elevated in SSc patients compared with healthy controls and correlated positively with the extent of skin fibrosis. Among the 21 patients with SSc in the longitudinal study, 7 had decreased BAFF levels, 11 had levels that remained unchanged, and 3 patients had increased levels. Decreasing BAFF levels were accompanied by regression of skin sclerosis, whereas increasing levels of BAFF were associated with the new onset or worsening of organ involvement. BAFF mRNA expression was up‐regulated in the affected skin of patients with early diffuse cutaneous SSc. BAFFR expression on B cells was increased in SSc patients relative to healthy controls. Furthermore, SSc B cells that were stimulated by BAFF exhibited an enhanced ability to produce IgG and IL‐6.Conclusion: These results suggest that BAFF and its signaling in B cells contribute to B cell abnormalities and disease development in patients with SSc.

Objective . Myositis-specific autoantibodies (MSAs) are a useful tool in diagnosis, defining clinical subsets and predicting prognosis of dermatomyositis (DM) and polymyositis (PM). In this study, we identified a novel MSA reactive with 155 and 140 kDa nuclear proteins [anti-155/140 antibody (Ab)] and determined the clinical feature of DM patients positive for this autoantibody (autoAb). Methods . Sera from 52 Japanese patients with DM, 9 with PM, 48 with systemic lupus erythematosus (SLE), 126 with systemic sclerosis and 18 with idiopathic interstitial pneumonia were examined by immunoprecipitation assays. Positive sera were further characterized by immunodepletion and immunofluorescence staining. Results . Seven of the 52 (13%) Japanese patients with DM immunoprecipitated 155 and 140 kDa proteins from ³⁵ S-labelled K562 leukaemia cell extract. No patients with SLE, systemic sclerosis or idiopathic interstitial pneumonia as well as healthy controls were positive for this autoAb. Patients with anti-155/140 Ab developed heliotrope rash, Gottron's papules or sign and flagellate erythema significantly more frequently than those negative. Notably, internal malignancy was found at significantly higher frequency in those positive than those negative (71 vs 11%; P < 0.005). In contrast, none of these patients positive for this autoAb had interstitial lung disease. Conclusions . This novel MSA is associated with cancer-associated DM and may serve as a diagnostic serological marker for this specific subset.

Objectives Myositis-specific autoantibodies (MSAs) are useful tools for identifying clinically homogeneous subsets and predicting prognosis of patients with idiopathic inflammatory myopathies (IIM) including polymyositis (PM) and dermatomyositis (DM). Recent studies have shown that anti-NXP2 antibody (Ab) is a major MSA in juvenile dermatomyositis (JDM). In this study the frequencies and clinical associations of anti-NXP2 Ab were evaluated in adult patients with IIM. Methods Clinical data and serum samples were collected from 507 adult Japanese patients with IIM (445 with DM and 62 with PM). Eleven patients with JDM, 108 with systemic lupus erythematosus, 433 with systemic sclerosis and 124 with idiopathic pulmonary fibrosis were assessed as disease controls. Serum was examined for anti-NXP2 Ab by immunoprecipitation and western blotting using polyclonal anti-NXP2 Ab. Results Seven patients (1.6%) with adult DM and one (1.6%) with adult PM were positive for anti-NXP2 Ab. Except for two patients with JDM, none of the disease controls were positive for this autoantibody. Among eight adult patients with IIM, three had internal malignancies within 3 years of diagnosis of IIM. Another patient with DM also had a metastatic cancer at the diagnosis. All of the carcinomas were at an advanced stage (stage IIIb–IV). Conclusions While less common than in juvenile IIM, anti-NXP2 Ab was found in adult IIM. Anti-NXP2 Ab may be associated with adult IIM with malignancy.