ObjectiveTo identify similarities and differences in the clinical features of adult Japanese patients with individual anti-aminoacyl-tRNA synthetase antibodies (anti-ARS Abs).MethodsThis 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.ResultsAnti-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.ConclusionPatients 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.”

To clarify the association of clinical and prognostic features with dermatomyositis (DM)specific autoantibodies (Abs) in adult Japanese patients with 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 1␣ (TIF-1␣), TIF-1␤, and TIF-1␥. The clinical associations of antigen reactivity were also evaluated.Results. Anti-155/140-positive sera reacted with 140-kd TIF-1␣ in addition to 155-kd TIF-1␥. Among sera from 456 DM patients, 52 were reactive with both TIF-1␣ and TIF-1␥, while another 25 were reactive with TIF-1␥ alone. Additionally, 7 were reactive with TIF-1␤. Malignancy was more frequently found in adult patients with both anti-TIF-1␣ and anti-TIF-1␥ antibodies than in those with anti-TIF-1␥ 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-1␣ and TIF-1␤, in addition to TIF-1␥. Since TIF-1 proteins have significant roles in oncogenesis, these antibodies may be produced during misdirected antitumor immunity.Polymyositis (PM) and dermatomyositis (DM) are idiopathic inflammatory disorders that mainly affect the muscle and/or skin (1). Clinical manifestations of PM/DM are heterogeneous, with varying degrees of myositis, skin rash, and accompanying symptoms such as interstitial lung disease and internal malignancy. The association of malignancy with PM/DM, which is termed cancer-associated myositis, is well appreciated, particularly in patients with DM (2-6). Since malignant disease is one of the main causes of mortality in these patients, diagnosing occult cancer in them is important and challenging for clinicians.

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. Autoantibodies against DFS70 (dense fine speckles 70) antigen (also known as lens epithelium-derived growth factor) have been recently identified among the antinuclear antibodies (ANAs) in patients with atopic disorders. We undertook this study to examine the frequency of anti-DFS70 antibodies in a large number of healthy people.Methods. Sera of 597 healthy individuals working in a hospital (142 men, 455 women) were analyzed for ANAs and for anti-DFS70 antibodies by indirect immunofluorescence (IIF) with HEp-2 cells as a substrate and by immunoblotting using DFS70 recombinant protein and whole HeLa cell extract.Results. ANAs were present in 20% of all individuals by IIF. Nine percent of subjects were ANA positive at a serum dilution of 1:40, 4.0% at 1:80, 5.5% at 1:160, 1.0% at 1:320, and 0.3% at 1:640. There were 64 anti-DFS70 antibody-positive individuals. Surprisingly, this was 11% of the whole population and 54% of the ANA-positive population. The percentage of female anti-DFS70 antibody-positive subjects (86%; 55 of 64 subjects) was higher than the percentage of female anti-DFS70 antibody-negative subjects (75%; 398 of 533 subjects) (P < 0.05). The prevalence of anti-DFS70 antibody-positive sera decreased with increasing age (P ‫؍‬ 0.0017).Conclusion. Considering that anti-DFS70 antibody positivity is rare in patients with systemic autoimmune diseases, introducing the anti-DFS70 antibody examination as a screening test for ANA-positive persons could be used to rule out systemic autoimmune diseases, resulting in considerable cost-saving potential. In addition, this test defines a subpopulation of healthy people in whom long-term followup might reveal healthrelated implications of this finding, since anti-DFS70 antibodies have been shown to be associated with some illnesses.