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Abstract Number: 0417

Different Immunophenotypes Characterized IgG4-Related Disease Clinical Phenotypes

Eduardo Martin-Nares1, Janette Furuzawa-Carballeda1, Ángel Alexis Priego-Ranero1, Isela Chan-Campos1, Gladys Sulikey Herrera-Noguera1, Fidel López-Verdugo1 and Gabriela Hernandez-Molina1, 1Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Distrito Federal, Mexico

Meeting: ACR Convergence 2020

Keywords: autoimmune diseases, Fibrosing syndromes, IgG4 Related Disease, Miscellaneous Rheumatic and Inflammatory Diseases, T-Lymphocyte

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Session Information

Date: Friday, November 6, 2020

Session Title: Vasculitis – Non-ANCA-Associated & Related Disorders Poster I

Session Type: Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Patients with IgG4-related disease (IgG4-RD) can be classified in clinical phenotypes which differ in terms of demographics, clinical and serological features. Whether there are also differences in the immunophenotype of each phenotype is unknown. Our aim was to characterize the immunophenotype of IgG4-RD patients according to their clinical phenotype.

Methods: We included consecutive patients with a diagnosis of IgG4-RD according to the Comprehensive Diagnostic Criteria for IgG4-RD who attended our Institution from Aug 2018 to Nov 2019. Healthy subjects were included as controls. We obtained peripheral blood for isolation of peripheral mononuclear cells and through negative selection, CD4+ memory T cells were obtained. We determined the percentage of the following cell subsets by flow cytometry:

  • Th2 (CD4+/CD45RO+/CD14-/IL-4+; CD4+/CD45RO+/CD14-/IL-13+, CD4+/CD45RO+/CD14-/IL-5+);
  • CD4+IL-21 T cells (CD4+/CD45RO+/CD14-/IL-21+);
  • CD4+ cytotoxic T cells (CTLs) (CD4+/CD45RO+/SLAMF7+/IL-1β+/TGF-β1+);
  • Th9 (CD3+/CD4+/ CD45RO+/IL-9);
  • T follicular helper cells (Tfh) (CD4+/CD45RO+/CCR7-/ICOS+/CCCR5+/Bcl6+);
  • Tfh1 (CD4+/CD45RO+/CCR7-/ICOS+/CCCR5+/Bcl6+/IFN-γ+);
  • Tfh2 (CD4+/CD45RO+/CCR7-/ICOS+/CCCR5+/Bcl6+/IL-4+);
  • Tfh17 (CD4+/CD45RO+/CCR7-/ICOS+/CCCR5+/Bcl6+/IL-17+);
  • Tfr (CD4+/CD45RO+/CCR7-/ICOS+/CCCR5+/Bcl6+/Foxp3+);
  • Tregs (CD4+/CD25hi/CD127-/Foxp3+);
  • Tr1 (CD4+/CD25low/Foxp3-/IL-10+);
  • Th3 (CD4+/CD25-/Foxp3-/TGF-β1+);
  • Bregs (CD19+/CD24hi/CD38hi/IL-10+);
  • Plasmocitoid dendritic cells (pDC) (CD86+/CD163hi/IL-10+);
  • M1 macrophages (CD86+/CD127+/TNF-α+);
  • M2 macrophages (CD163+/CD14+/TGF-β1+/IL-33+).

Results: We recruited 43 patients with a mean age of 52.3±16.4 years, 48.8% were male. Twelve controls were included. Eight (18.6%) patients belong to the pancreato-hepatobiliary, 7 (16.3%) to the retroperitoneal-aorta, 16 (37.2%) to the head and neck limited and 12 (27.9%) to the Mikulicz/Systemic phenotypes. Twenty two (51.2%) had active disease. The percentages of all cell subsets were statistically higher in patients vs controls, with the exception of Tr1 cells. The percentages of the following cell subsets were different among clinical phenotypes: Th2 (CD4+/IL-4+) (p=0.029), Th2 (CD4+/IL-5+) (p=0.047), CD4+ CTLs, (p=< 0.001), Tfh17 (p=0.005), Tregs FOXP3+ (p=0.008), Th3 (p=0.02), Bregs (p=0.005) and pDC IL-10 (p=0.016). In a sensitive analysis including only the 22 patients with active disease, the same cell subsets remained significant and we also observed differences in Tfh1 (p=0.03), Tfh2 (p=0.009), Tr1 (p=0.034), and M1 macrophages (p=0.03). Patients with active IgG4-RD had higher proportions of Tfh (< 0.001), Tfh17 (p< 0.001), Tr1 (p=0.001), Th3 (p=0.01), pDC IL-10 (0.005) and M1 macrophages (p=0.017). There were no differences according to the presence of atopy or immunosuppressive treatment at recruitment.

Conclusion: Our study showed that the clinical heterogeneity of IgG4-RD might be driven by the participation of different immune cell subsets.


Disclosure: E. Martin-Nares, None; J. Furuzawa-Carballeda, None; �. Priego-Ranero, None; I. Chan-Campos, None; G. Herrera-Noguera, None; F. López-Verdugo, None; G. Hernandez-Molina, None.

To cite this abstract in AMA style:

Martin-Nares E, Furuzawa-Carballeda J, Priego-Ranero �, Chan-Campos I, Herrera-Noguera G, López-Verdugo F, Hernandez-Molina G. Different Immunophenotypes Characterized IgG4-Related Disease Clinical Phenotypes [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/different-immunophenotypes-characterized-igg4-related-disease-clinical-phenotypes/. Accessed July 4, 2022.
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