Immune Profile Differences Between IgG4-Related Diseases and Primary Sjögren's Syndrome

Overview

Journal J Inflamm Res

Publisher Dove Medical Press

Date 2025 Jan 28

PMID 39871956

Authors

Yan Qin

Lili Shang

Yanlin Wang

Min Feng

Zhaojun Liang

Nan Wang

Chong Gao

Jing Luo

Affiliations

Soon will be listed here.

Abstract

Purpose: Immunoglobulin G4-related disease (IgG4-RD) share clinical features with primary Sjögren's syndrome (pSS). This study aimed to identify altered serological parameters and potential biomarkers of IgG4-RD and pSS.

Methods: Forty IgG4-RD patients, 40 pSS patients, and 40 healthy controls (HC) were enrolled in this study. Routine serological parameters and clinical manifestations were assessed. IgG subclasses (IgGSc) were detected using a Siemens BN P, and lymphocyte subsets were analyzed using flow cytometry. Cytokines assays were performed using cytometric bead array.

Results: Compared to pSS, IgG4-RD patients had higher IgG4 ( <0.001) and lower IgG1 ( =0.014). The natural killer (NK) cells ( = 0.004), CD4+ T cells ( = 0.028), and TBNK cells ( = 0.040) were increased in IgG4-RD compared to pSS. IgG4 used to differentiate IgG4-RD from pSS produced an area under the curve (AUC) of up to 0.952. In addition, we compared serum parameters, immune cells, and cytokines of IgG4-RDwith mouth dryness or eye dryness with those of pSS with the same symptoms, and similar serological changes were observed. IgG4-RD patients with mouth dryness had higher IgG4 ( <0.001) and Th cells ( = 0.016) but lower IgG1 ( = 0.009) compared to pSS with dry mouth. IgG4-RD patients with eye dryness had higher levels of IgG4 ( <0.001), Treg cells ( = 0.037), and NK cells ( = 0.017) than pSS patients with eye dryness. Moreover, IgG4-RD patients with mouth and eye dryness had higher levels of B ( = 0.006), Th ( = 0.026), Th2 ( = 0.007), and Treg cells ( = 0.028) than IgG4-RD patients without mouth and eye dryness.

Conclusion: Immune system disorder is an outstanding feature of IgG4-RD, and its feature differ from pSS. Assessment of immune status is important in the diagnosis and differential diagnosis of IgG4-RD.

References

Feng M, Guo H, Zhang C, Wang Y, Liang Z, Zhao X . Absolute reduction of regulatory T cells and regulatory effect of short-term and low-dose IL-2 in polymyositis or dermatomyositis. Int Immunopharmacol. 2019; 77:105912. DOI: 10.1016/j.intimp.2019.105912. View

Martin-Nares E, Hernandez-Molina G, Baenas D, Paira S . IgG4-Related Disease: Mimickers and Diagnostic Pitfalls. J Clin Rheumatol. 2021; 28(2):e596-e604. DOI: 10.1097/RHU.0000000000001787. View

Culver E, Sadler R, Simpson D, Cargill T, Makuch M, Bateman A . Elevated Serum IgG4 Levels in Diagnosis, Treatment Response, Organ Involvement, and Relapse in a Prospective IgG4-Related Disease UK Cohort. Am J Gastroenterol. 2016; 111(5):733-43. DOI: 10.1038/ajg.2016.40. View

Lecuit M, Aucouturier P, Abbas A, Cadranel J, Silvain C, Berthelot J . Overexpression of IgG2 in patients resembling IgG4-related disease with normal IgG4. Scand J Immunol. 2021; 95(3):e13126. DOI: 10.1111/sji.13126. View

Yan S, Peng Y, Wu Z, Cheng L, Li H, Xu H . Distinct metabolic biomarkers to distinguish IgG4-related disease from Sjogren's syndrome and pancreatic cancer and predict disease prognosis. BMC Med. 2022; 20(1):497. PMC: 9795602. DOI: 10.1186/s12916-022-02700-x. View

Wallace Z, Deshpande V, Mattoo H, Mahajan V, Kulikova M, Pillai S . IgG4-Related Disease: Clinical and Laboratory Features in One Hundred Twenty-Five Patients. Arthritis Rheumatol. 2015; 67(9):2466-75. PMC: 4621270. DOI: 10.1002/art.39205. View

Chen Y, Lin W, Yang H, Wang M, Zhang P, Feng R . Aberrant Expansion and Function of Follicular Helper T Cell Subsets in IgG4-Related Disease. Arthritis Rheumatol. 2018; 70(11):1853-1865. PMC: 6220938. DOI: 10.1002/art.40556. View

Tanaka A, Moriyama M, Nakashima H, Miyake K, Hayashida J, Maehara T . Th2 and regulatory immune reactions contribute to IgG4 production and the initiation of Mikulicz disease. Arthritis Rheum. 2011; 64(1):254-63. DOI: 10.1002/art.33320. View

Hasegawa K, Hanayama Y, Obika M, Miyoshi T, Ogawa H, Kondo E . Clinical and biochemical characteristics of patients having general symptoms with increased serum IgG4. Mod Rheumatol. 2019; 30(4):721-728. DOI: 10.1080/14397595.2019.1642291. View

10.

Victora G, Nussenzweig M . Germinal Centers. Annu Rev Immunol. 2022; 40:413-442. DOI: 10.1146/annurev-immunol-120419-022408. View

11.

Koupenova M, Clancy L, Corkrey H, Freedman J . Circulating Platelets as Mediators of Immunity, Inflammation, and Thrombosis. Circ Res. 2018; 122(2):337-351. PMC: 5777300. DOI: 10.1161/CIRCRESAHA.117.310795. View

12.

Mizushima I, Konishi M, Sanada H, Suzuki K, Takeji A, Zoshima T . Serum IgG4 levels at diagnosis can predict unfavorable outcomes of untreated patients with IgG4-related disease. Sci Rep. 2021; 11(1):13341. PMC: 8233326. DOI: 10.1038/s41598-021-92814-8. View

13.

Rao D, Gurish M, Marshall J, Slowikowski K, Fonseka C, Liu Y . Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis. Nature. 2017; 542(7639):110-114. PMC: 5349321. DOI: 10.1038/nature20810. View

14.

Martin-Nares E, Hernandez-Molina G, Priego-Ranero A, Chan-Campos I, Herrera-Noguera G, Lopez-Verdugo F . Peripheral Immunophenotype in IgG4-Related Disease and Its Association with Clinical Phenotypes and Disease Activity. Cells. 2023; 12(4). PMC: 9954418. DOI: 10.3390/cells12040670. View

15.

Kwon O, Park M, Kim Y . Correlation between serologic parameters and disease activity of IgG4-related disease: Differences between patients with normal and elevated serum IgG4 concentrations. Front Immunol. 2022; 13:1020459. PMC: 9608652. DOI: 10.3389/fimmu.2022.1020459. View

16.

Quast I, Dvorscek A, Pattaroni C, Steiner T, McKenzie C, Pitt C . Interleukin-21, acting beyond the immunological synapse, independently controls T follicular helper and germinal center B cells. Immunity. 2022; 55(8):1414-1430.e5. DOI: 10.1016/j.immuni.2022.06.020. View

17.

Szabo K, Jambor I, Szanto A, Horvath I, Tarr T, Nakken B . The Imbalance of Circulating Follicular T Helper Cell Subsets in Primary Sjögren's Syndrome Associates With Serological Alterations and Abnormal B-Cell Distribution. Front Immunol. 2021; 12:639975. PMC: 8018236. DOI: 10.3389/fimmu.2021.639975. View

18.

Ming B, Zhong J, Dong L . Role of eosinophilia in IgG4-related disease. Clin Exp Rheumatol. 2021; 40(5):1038-1044. DOI: 10.55563/clinexprheumatol/l7se2n. View

19.

Murayama K, Ikegami I, Kamekura R, Sakamoto H, Yanagi M, Kamiya S . CD4CD8 T follicular helper cells regulate humoral immunity in chronic inflammatory lesions. Front Immunol. 2022; 13:941385. PMC: 9452889. DOI: 10.3389/fimmu.2022.941385. View

20.

Sohn K, Ham J, Chung S, Kang H, Kim H . Analysis of Innate and Adaptive Immunological Characteristics in Patients with IgG4-Related Disease. Int Arch Allergy Immunol. 2020; 181(10):807-812. PMC: 7592937. DOI: 10.1159/000508699. View