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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2024

Open Access 01-12-2024 | Dermatomyositis | Research

Elevated serum B-cell activator factor levels predict rapid progressive interstitial lung disease in anti-melanoma differentiation associated protein 5 antibody positive dermatomyositis

Authors: Yumeng Shi, Hanxiao You, Chang Liu, Yulu Qiu, Chengyin Lv, Yujing Zhu, Lingxiao Xu, Fang Wang, Miaojia Zhang, Wenfeng Tan

Published in: Orphanet Journal of Rare Diseases | Issue 1/2024

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Abstract

Background

Rapid progressive interstitial lung disease (RP-ILD) is the leading cause of anti-melanoma differentiation associated protein 5 antibody positive dermatomyositis (anti-MDA5+DM) related death. Elevated serum B-cell activating factor (BAFF) levels have been implicated in connective tissue diseases associated ILD. Here, we evaluate whether BAFF could be a prognostic biomarker for predicting RP-ILD in anti-MDA5+DM patients.

Methods

Serums were collected from 39 patients with anti-MDA5+DM (20 with RP-ILD and 19 with non-RP-ILD), 20 antisynthase syndrome (ASS) patients and 20 healthy controls (HC). BAFF concentration was measured by an enzyme-linked immunosorbent assay.

Results

Serum BAFF level was higher in anti-MDA5+DM patients than those in ASS patients and HC (3882.32 ± 1880.09 vs. 2540.89 ± 1403.04 and 2486.28 ± 767.97 pg/mL, p = 0.0056 and 0.0038, respectively). Within anti-MDA5+DM groups, RP-ILD patients exhibited higher BAFF concentration than non-RP-ILD group (4549.78 ± 1839.97 vs. 3297.28 ± 1794.69 pg/mL, p = 0.04). The BAFF concentration was positively correlated with levels of C-reactive protein (CRP), dehydrogenase (LDH) and cytokeratin (CK) in anti-MDA5+DM patients (r = 0.350, p = 0.035; r = 0.393, p = 0.016; r = 0.518, p = 0.001; respectively). The best cut-off value of BAFF concentration was 2971.5 pg/mL by ROC curve (AUC area = 0.690, p = 0.045) and BAFF > 2971.5 pg/mL was an independent risk factor for RP-ILD using multivariate analysis (OR = 9.389, 95% CI = 1.609—54.769; p = 0.013).

Conclusions

Serum BAFF could be a useful prognostic biomarker for early detecting RP-ILD risk in anti-MDA5+DM patients.
Literature
1.
Sato S, Hirakata M, Kuwana M, Suwa A, Inada S, Mimori T, et al. Autoantibodies to a 140-kd polypeptide, CADM-140, in Japanese patients with clinically amyopathic dermatomyositis. Arthritis Rheum. 2005;52(5):1571–6.CrossRefPubMed
2.
Sato S, Hoshino K, Satoh T, Fujita T, Kawakami Y, Fujita T, et al. RNA helicase encoded by melanoma differentiation-associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: association with rapidly progressive interstitial lung disease. Arthritis Rheum. 2009;60(7):2193–200.CrossRefPubMed
3.
Nakashima R, Imura Y, Kobayashi S, Yukawa N, Yoshifuji H, Nojima T, et al. The RIG-I-like receptor IFIH1/MDA5 is a dermatomyositis-specific autoantigen identified by the anti-CADM-140 antibody. Rheumatology (Oxford). 2010;49(3):433–40.CrossRefPubMed
4.
Hamaguchi Y, Kuwana M, Hoshino K, Hasegawa M, Kaji K, Matsushita T, et al. Clinical correlations with dermatomyositis-specific autoantibodies in adult Japanese patients with dermatomyositis: a multicenter cross-sectional study. Arch Dermatol. 2011;147(4):391–8.CrossRefPubMed
5.
Koga T, Fujikawa K, Horai Y, Okada A, Kawashiri SY, Iwamoto N, et al. The diagnostic utility of anti-melanoma differentiation-associated gene 5 antibody testing for predicting the prognosis of Japanese patients with DM. Rheumatology (Oxford). 2012;51(7):1278–84.CrossRefPubMed
6.
Kumric M, Zivkovic PM, Ticinovic Kurir T, Vrdoljak J, Vilovic M, Martinovic D, et al. Role of B-Cell Activating Factor (BAFF) in inflammatory bowel disease. Diagnostics (Basel). 2021;12(1):45.CrossRefPubMed
7.
Singh H, Kumar U, Senapati S. Translational implications of humoral and cellular immune dysfunction in granulomatosis with polyangiitis. Cytokine. 2023;164:156154.CrossRefPubMed
8.
Saez Moya M, Gutierrez-Cozar R, Punet-Ortiz J, Rodriguez de la Concepcion ML, Blanco J, Carrillo J, et al. Autoimmune B Cell repertoire in a Mouse Model of Sjogren’s syndrome. Front Immunol. 2021;12:666545.CrossRefPubMedPubMedCentral
9.
Erazo-Martinez V, Tobon GJ, Canas CA. Circulating and skin biopsy-present cytokines related to the pathogenesis of cutaneous lupus erythematosus. Autoimmun Rev. 2023;22(2):103262.CrossRefPubMed
10.
11.
Hamada T, Samukawa T, Kumamoto T, Hatanaka K, Tsukuya G, Yamamoto M, et al. Serum B cell-activating factor (BAFF) level in connective tissue disease associated interstitial lung disease. BMC Pulm Med. 2015;15:110.CrossRefPubMedPubMedCentral
12.
Wang Y, Xie X, Zheng S, Du G, Chen S, Zhang W, et al. Serum B-cell activating factor and lung ultrasound B-lines in connective tissue disease related interstitial lung disease. Front Med (Lausanne). 2022;9:1066111.CrossRefPubMed
13.
Francois A, Chatelus E, Wachsmann D, Sibilia J, Bahram S, Alsaleh G, et al. B lymphocytes and B-cell activating factor promote collagen and profibrotic markers expression by dermal fibroblasts in systemic sclerosis. Arthritis Res Ther. 2013;15(5):R168.CrossRefPubMedPubMedCentral
14.
Matsushita T, Kobayashi T, Kano M, Hamaguchi Y, Takehara K. Elevated serum B-cell activating factor levels in patients with dermatomyositis: association with interstitial lung disease. J Dermatol. 2019;46(12):1190–6.CrossRefPubMed
15.
Shen N, Zhou X, Jin X, Lu C, Hu X, Zhang Y, et al. MDA5 expression is associated with TGF-β-induced fibrosis: potential mechanism of interstitial lung disease in anti-MDA5 dermatomyositis. Rheumatology (Oxford). 2022;62(1):373–83.CrossRefPubMed
16.
Kobayashi N, Kobayashi I, Mori M, Sato S, Iwata N, Shigemura T, et al. Increased serum B cell activating factor and a proliferation-inducing ligand are associated with interstitial lung disease in patients with juvenile dermatomyositis. J Rheumatol. 2015;42(12):2412–8.CrossRefPubMed
17.
Krystufkova O, Hulejova H, Mann HF, Pecha O, Putova I, Ekholm L, et al. Serum levels of B-cell activating factor of the TNF family (BAFF) correlate with anti-Jo-1 autoantibodies levels and disease activity in patients with anti-Jo-1positive polymyositis and dermatomyositis. Arthritis Res Ther. 2018;20(1):158.CrossRefPubMedPubMedCentral
18.
Gono T, Masui K, Nishina N, Kawaguchi Y, Kawakami A, Ikeda K, et al. Risk prediction modeling based on a combination of initial serum biomarker levels in polymyositis/dermatomyositis-associated interstitial lung disease. Arthritis Rheumatol. 2021;73(4):677–86.CrossRefPubMed
19.
Xu Y, Yang CS, Li YJ, Liu XD, Wang JN, Zhao Q, et al. Predictive factors of rapidly progressive-interstitial lung disease in patients with clinically amyopathic dermatomyositis. Clin Rheumatol. 2016;35(1):113–6.CrossRefPubMed
20.
Feng L, Wang H, Zhao Y, Zhao T, Zhang J, Huang F, et al. Clinical manifestations and outcome of anti-aminoacyl-transfer RNA synthetase antibody and anti-melanoma differentiation-associated gene 5 antibody positive patients with interstitial lung disease. Clin Exp Rheumatol. 2022;40(1):97–103.CrossRefPubMed
21.
Wang Y, Zhu L, Ju B, Luo J, Li Q, Lv X, et al. Alterations of peripheral blood B cell subsets in Chinese patients with adult idiopathic inflammatory myopathies. Clin Exp Rheumatol. 2022;40(2):260–6.CrossRefPubMed
22.
He C, Li W, Xie Q, Yin G. Rituximab in the treatment of interstitial lung diseases related to anti-melanoma differentiation-associated gene 5 dermatomyositis: a systematic review. Front Immunol. 2021;12:820163.CrossRefPubMed
23.
Mariette X, Roux S, Zhang J, Bengoufa D, Lavie F, Zhou T, et al. The level of BLyS (BAFF) correlates with the titre of autoantibodies in human Sjogren’s syndrome. Ann Rheum Dis. 2003;62(2):168–71.CrossRefPubMedPubMedCentral
24.
Stohl W, Metyas S, Tan SM, Cheema GS, Oamar B, Roschke V, et al. Inverse association between circulating APRIL levels and serological and clinical disease activity in patients with systemic lupus erythematosus. Ann Rheum Dis. 2004;63(9):1096–103.CrossRefPubMedPubMedCentral
25.
Matsushita T, Hasegawa M, Yanaba K, Kodera M, Takehara K, Sato S. Elevated serum BAFF levels in patients with systemic sclerosis: enhanced BAFF signaling in systemic sclerosis B lymphocytes. Arthritis Rheum. 2006;54(1):192–201.CrossRefPubMed
26.
Vosters JL, Roescher N, Polling EJ, Illei GG, Tak PP. The expression of APRIL in Sjogren’s syndrome: aberrant expression of APRIL in the salivary gland. Rheumatology (Oxford). 2012;51(9):1557–62.CrossRefPubMed
27.
Krystufkova O, Vallerskog T, Helmers SB, Mann H, Putova I, Belacek J, et al. Increased serum levels of B cell activating factor (BAFF) in subsets of patients with idiopathic inflammatory myopathies. Ann Rheum Dis. 2009;68(6):836–43.CrossRefPubMed
28.
Baek A, Park HJ, Na SJ, Shim DS, Moon JS, Yang Y, et al. The expression of BAFF in the muscles of patients with dermatomyositis. J Neuroimmunol. 2012;249(1–2):96–100.CrossRefPubMed
29.
Lopez De Padilla CM, McNallan KT, Crowson CS, Bilgic H, Bram RJ, Hein MS, et al. BAFF expression correlates with idiopathic inflammatory myopathy disease activity measures and autoantibodies. J Rheumatol. 2013;40(3):294–302.CrossRefPubMed
30.
Maglione PJ, Gyimesi G, Cols M, Radigan L, Ko HM, Weinberger T, et al. BAFF-driven B cell hyperplasia underlies lung disease in common variable immunodeficiency. JCI Insight. 2019;4(5):e122728.CrossRefPubMedPubMedCentral
31.
Matson EM, Abyazi ML, Bell KA, Hayes KM, Maglione PJ. B cell dysregulation in common variable immunodeficiency interstitial lung disease. Front Immunol. 2020;11:622114.CrossRefPubMed
32.
Xu L, You H, Wang L, Lv C, Yuan F, Li J, et al. Identification of three different phenotypes in anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis patients: implications for prediction of rapidly progressive interstitial lung disease. Arthritis Rheumatol. 2023;75(4):609–19.CrossRefPubMed
33.
Wu W, Xu W, Sun W, Zhang D, Zhao J, Luo Q, et al. Forced vital capacity predicts the survival of interstitial lung disease in anti-MDA5 positive dermatomyositis: a multi-centre cohort study. Rheumatology (Oxford). 2021;61(1):230–9.CrossRefPubMed
Metadata
Title
Elevated serum B-cell activator factor levels predict rapid progressive interstitial lung disease in anti-melanoma differentiation associated protein 5 antibody positive dermatomyositis
Authors
Yumeng Shi
Hanxiao You
Chang Liu
Yulu Qiu
Chengyin Lv
Yujing Zhu
Lingxiao Xu
Fang Wang
Miaojia Zhang
Wenfeng Tan
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2024
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-024-03153-6

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