ObjectivesThe purpose of this study was to investigate the baseline independent risk factors for predicting 6-month mortality of patients with anti-melanoma differentiation-associated gene 5 (anti-MDA5)-positive dermatomyositis (DM) and develop a matrix prediction model formed by these risk factors.MethodsThe hospitalized patients with DM who completed at least 6-month follow-up were recruited as a derivation cohort. The primary exposure was defined as positive anti-MDA5 at the baseline. The primary outcome was all-cause 6-month mortality after enrollment. A matrix prediction model was developed in the derivation cohort, and another published cohort was used for external validation.ResultsIn derivation cohort, 82 patients with DM were enrolled (mean age of onset 50 ± 11 years and 63% women), with 40 (49%) showing positive anti-MDA5. Gottron sign/papules (OR: 5.135, 95%CI: 1.489–17.708), arthritis (OR: 5.184, 95%CI: 1.455–18.467), interstitial lung disease (OR: 7.034, 95%CI: 1.157–42.785), and higher level of C4 (OR: 1.010, 95%CI: 1.002–1.017) were the independent associators with positive anti-MDA5 in patients with DM. Patients with anti-MDA5-positive DM had significant higher 6-month all-cause mortality than those with anti-MDA5-negative (30 vs. 0%). Among the patients with anti-MDA5-positive DM, compared to the survivors, non-survivors had significantly advanced age of onset (59 ± 6 years vs. 46 ± 9 years), higher rates of fever (75 vs. 18%), positive carcinoma embryonic antigen (CEA, 75 vs. 14%), higher level of ferritin (median 2,858 ug/L vs. 619 ug/L, all p < 0.05). A stepwise multivariate Cox regression showed that ferritin ≥1,250 μg/L (HR: 10.4, 95%CI: 1.8–59.9), fever (HR: 11.2, 95%CI: 2.5–49.9), and positive CEA (HR: 5.2, 95%CI: 1.0–25.7) were the independent risk factors of 6-month mortality. A matrix prediction model was built to stratify patients with anti-MDA5-positive DM into different subgroups with various probabilities of 6-month mortality risk. In an external validation cohort, the observed 6-month all-cause mortality was 78% in high-risk group, 43% in moderate-risk group, and 25% in low-risk group, which shows good accuracy of the model.ConclusionBaseline characteristics such as fever, ferritin ≥1,250 μg/L, and positive CEA are the independent risk factors for 6-month all-cause mortality in patients with anti-MDA5-positive DM. A novel matrix prediction model composed of these three clinical indicators is first proposed to provide a chance for the exploration of individual treatment strategies in anti-MDA5-positive DM subgroups with various probabilities of mortality risk.

Background:Passive transfer of ANA and anti-SSA has been reported in patients with common variable immunodeficiency disorder who received intravenous immunoglobulin (IVIG). IVIG is also recommended to treat some special or life-threatening rheumatic diseases.Objectives:This study was aimed to explore whether any extractable nuclear antibodies (ENAs) were transferred to these rheumatic patients who received IVIG therapy.Methods:IVIG products of three batches were tested for ANA by using indirect immunofluorescent assay, and for ENAs by using line immunoassay (LIA) and chemiluminescence immunoassay (CLIA). These IVIG products were administrated to rheumatic patients at a dose of 20g/d×3 days (day1 to day3). Serum samples of these patients before IVIG (day0) and after IVIG (day4, day8, day10, day12, and more than one month) were tested by using LIA and CLIA. Anti-SSA was also detected using ELISA.Results:In these IVIG products, ANA was positive at a titer of 1:640 (cytoplasmic speckled) and 1:80 (speckled). Among 14 types of ENAs that could be tested using LIA, anti-SSA, anti-Ro52, anti-mitochondrial M2, and anti-centromere B antibodies were clearly detectable in IVIG products (Table 1). Likewise, another assay CLIA also detected the same positive autoantibodies in these products. LIA showed the highest concentration in anti-mitochondrial M2, while CLIA showed the highest concentration in anti-mitochondrial M2 and anti-Ro52. One 31-year-old male patient who was diagnosed as SLE (Figure 1) and one 72-year-old male patients who was diagnosed as necrotizing myositis received these IVIG products. Anti-SSA, anti-Ro52, anti-mitochondrial M2, but not anti-centromere B, were positive in the day4 serum samples, although all of these antibodies were negative at baseline (day0). The concentration of these antibodies decreased gradually as days passed and became undetectable around one month after IVIG.Table 1.The concentration of autoantibodies in intravenous immunoglobulin productsanti-SSAanti-Ro-52anti-mitochondrial M2anti-centromere BCut-offLIA(grey value)20±328±369±1019±4≥11CLIA (U/ml)333±107444±86434±66390±89>20ELISA (U/ml)90±13NANANA>20LIA, line immunoassay; CLIA, chemiluminescence immunoassay; ELISA, enzyme linked immunosorbent assayConclusion:This study preliminarily reported transient positivity of anti-SSA, anti-Ro52, and anti-mitochondrial M2 in rheumatic patients maybe because the passive transfer of these antibodies from IVIG products to the patients, although the potential influence of this transfer on the rheumatic diseases remained unknown.Figure 1.The concentration of autoantibodies in a 31-year-old male SLE patient receiving intravenous immunoglobulin at a dose of 20g/d×3 days (day1 to day3). Serum samples of these patients before IVIG (day0) and after IVIG (day4, day8, day10, day12, and day51) were tested by using line immunoassay (LIA) and chemiluminescence immunoassay (CLIA). Anti-SSA was also detected using ELISA. The horizontal red lines were the corresponding cut-off values of each assay.Disclosure of Interests:None declared