Autoantibodies in patients with interleukin 12 receptor beta 1 deficiency

Vincenzo Ronca, Qu Bo Chen, Vasiliky Lygoura, Imen Ben-Mustapha, Zakera Shums, Mehdi Trifa, Marco Carbone, Clara Mancuso, Chiara Milani, Francesca Bernuzzi, Xiong Ma, Nourhen Agrebi, Gary L. Norman, Christopher Chang, M. Eric Gershwin, Mohamed Ridha Barbouche, Pietro Invernizzi

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Objective: Interleukin 12 receptor beta 1 (IL-12Rβ1) deficiency is a primary immunodeficiency that exposes affected individuals to an augmented risk of intracellular pathogen-mediated infections. The paradoxical presence of autoimmune manifestations in immune-deficient patients has been recognized, but the basis of this phenomenon is unclear, with the role of frequent infections being a possible trigger to break tolerance. Our study aimed to analyze extensively a profile of autoantibodies in a clinically well-defined case series of patients with IL-12Rβ1 deficiency. Methods: Eight patients with IL-12Rβ1 deficiency referred to Children's Medical Center in Tunis, Tunisia, during 1995-2012 were enrolled in the study. Sixteen age- and gender-matched blood donors served as controls. Serum, liver-related autoantibodies immunoglobulin (Ig)G, IgM, IgA were tested by ELISA and by standard indirect immunofluorescence on Hep-2 cells. Results: We found a significant prevalence of liver autoantibodies in the study group. Regarding primary biliary cholangitis (PBC), two of eight patients were positive for MIT3 autoantibodies, both confirmed by immunofluorescence, and one patient was positive for PBC-specific antinuclear antibodies, sp100. Moreover, two patients had significantly increased gamma-glutamyltransferase levels and one had IgM levels twice the upper limit of normal. Intriguingly two patients were positive for anti-actin antibodies; a typical feature of autoimmune hepatitis type 1, along with a significant increase in IgG levels. Conclusions: This is the first report of a serological analysis in patients with an IL-12Rβ1 deficiency. Despite the difficulty in interpreting the role of the IL-12, the evidence of liver-specific autoantibodies confirms the importance its signal in liver autoimmunity.

Original languageEnglish (US)
Pages (from-to)363-370
Number of pages8
JournalJournal of Digestive Diseases
Volume20
Issue number7
DOIs
StatePublished - Jul 1 2019

Fingerprint

Interleukin-12 Receptors
Autoantibodies
Cholangitis
Liver
Immunoglobulin M
Immunoglobulin G
Autoimmune Hepatitis
Tunisia
gamma-Glutamyltransferase
Antinuclear Antibodies
Interleukin-12
Indirect Fluorescent Antibody Technique
Infection
Blood Donors
Autoimmunity
Immunoglobulin A
Fluorescent Antibody Technique
Actins
Anti-Idiotypic Antibodies
Enzyme-Linked Immunosorbent Assay

Keywords

  • autoantibodies
  • autoimmunity
  • immunodeficiency
  • interleukin-12
  • interleukin-12-receptor deficiency

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Ronca, V., Chen, Q. B., Lygoura, V., Ben-Mustapha, I., Shums, Z., Trifa, M., ... Invernizzi, P. (2019). Autoantibodies in patients with interleukin 12 receptor beta 1 deficiency. Journal of Digestive Diseases, 20(7), 363-370. https://doi.org/10.1111/1751-2980.12790

Autoantibodies in patients with interleukin 12 receptor beta 1 deficiency. / Ronca, Vincenzo; Chen, Qu Bo; Lygoura, Vasiliky; Ben-Mustapha, Imen; Shums, Zakera; Trifa, Mehdi; Carbone, Marco; Mancuso, Clara; Milani, Chiara; Bernuzzi, Francesca; Ma, Xiong; Agrebi, Nourhen; Norman, Gary L.; Chang, Christopher; Gershwin, M. Eric; Barbouche, Mohamed Ridha; Invernizzi, Pietro.

In: Journal of Digestive Diseases, Vol. 20, No. 7, 01.07.2019, p. 363-370.

Research output: Contribution to journalArticle

Ronca, V, Chen, QB, Lygoura, V, Ben-Mustapha, I, Shums, Z, Trifa, M, Carbone, M, Mancuso, C, Milani, C, Bernuzzi, F, Ma, X, Agrebi, N, Norman, GL, Chang, C, Gershwin, ME, Barbouche, MR & Invernizzi, P 2019, 'Autoantibodies in patients with interleukin 12 receptor beta 1 deficiency', Journal of Digestive Diseases, vol. 20, no. 7, pp. 363-370. https://doi.org/10.1111/1751-2980.12790
Ronca V, Chen QB, Lygoura V, Ben-Mustapha I, Shums Z, Trifa M et al. Autoantibodies in patients with interleukin 12 receptor beta 1 deficiency. Journal of Digestive Diseases. 2019 Jul 1;20(7):363-370. https://doi.org/10.1111/1751-2980.12790
Ronca, Vincenzo ; Chen, Qu Bo ; Lygoura, Vasiliky ; Ben-Mustapha, Imen ; Shums, Zakera ; Trifa, Mehdi ; Carbone, Marco ; Mancuso, Clara ; Milani, Chiara ; Bernuzzi, Francesca ; Ma, Xiong ; Agrebi, Nourhen ; Norman, Gary L. ; Chang, Christopher ; Gershwin, M. Eric ; Barbouche, Mohamed Ridha ; Invernizzi, Pietro. / Autoantibodies in patients with interleukin 12 receptor beta 1 deficiency. In: Journal of Digestive Diseases. 2019 ; Vol. 20, No. 7. pp. 363-370.
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AU - Ronca, Vincenzo

AU - Chen, Qu Bo

AU - Lygoura, Vasiliky

AU - Ben-Mustapha, Imen

AU - Shums, Zakera

AU - Trifa, Mehdi

AU - Carbone, Marco

AU - Mancuso, Clara

AU - Milani, Chiara

AU - Bernuzzi, Francesca

AU - Ma, Xiong

AU - Agrebi, Nourhen

AU - Norman, Gary L.

AU - Chang, Christopher

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AU - Barbouche, Mohamed Ridha

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N2 - Objective: Interleukin 12 receptor beta 1 (IL-12Rβ1) deficiency is a primary immunodeficiency that exposes affected individuals to an augmented risk of intracellular pathogen-mediated infections. The paradoxical presence of autoimmune manifestations in immune-deficient patients has been recognized, but the basis of this phenomenon is unclear, with the role of frequent infections being a possible trigger to break tolerance. Our study aimed to analyze extensively a profile of autoantibodies in a clinically well-defined case series of patients with IL-12Rβ1 deficiency. Methods: Eight patients with IL-12Rβ1 deficiency referred to Children's Medical Center in Tunis, Tunisia, during 1995-2012 were enrolled in the study. Sixteen age- and gender-matched blood donors served as controls. Serum, liver-related autoantibodies immunoglobulin (Ig)G, IgM, IgA were tested by ELISA and by standard indirect immunofluorescence on Hep-2 cells. Results: We found a significant prevalence of liver autoantibodies in the study group. Regarding primary biliary cholangitis (PBC), two of eight patients were positive for MIT3 autoantibodies, both confirmed by immunofluorescence, and one patient was positive for PBC-specific antinuclear antibodies, sp100. Moreover, two patients had significantly increased gamma-glutamyltransferase levels and one had IgM levels twice the upper limit of normal. Intriguingly two patients were positive for anti-actin antibodies; a typical feature of autoimmune hepatitis type 1, along with a significant increase in IgG levels. Conclusions: This is the first report of a serological analysis in patients with an IL-12Rβ1 deficiency. Despite the difficulty in interpreting the role of the IL-12, the evidence of liver-specific autoantibodies confirms the importance its signal in liver autoimmunity.

AB - Objective: Interleukin 12 receptor beta 1 (IL-12Rβ1) deficiency is a primary immunodeficiency that exposes affected individuals to an augmented risk of intracellular pathogen-mediated infections. The paradoxical presence of autoimmune manifestations in immune-deficient patients has been recognized, but the basis of this phenomenon is unclear, with the role of frequent infections being a possible trigger to break tolerance. Our study aimed to analyze extensively a profile of autoantibodies in a clinically well-defined case series of patients with IL-12Rβ1 deficiency. Methods: Eight patients with IL-12Rβ1 deficiency referred to Children's Medical Center in Tunis, Tunisia, during 1995-2012 were enrolled in the study. Sixteen age- and gender-matched blood donors served as controls. Serum, liver-related autoantibodies immunoglobulin (Ig)G, IgM, IgA were tested by ELISA and by standard indirect immunofluorescence on Hep-2 cells. Results: We found a significant prevalence of liver autoantibodies in the study group. Regarding primary biliary cholangitis (PBC), two of eight patients were positive for MIT3 autoantibodies, both confirmed by immunofluorescence, and one patient was positive for PBC-specific antinuclear antibodies, sp100. Moreover, two patients had significantly increased gamma-glutamyltransferase levels and one had IgM levels twice the upper limit of normal. Intriguingly two patients were positive for anti-actin antibodies; a typical feature of autoimmune hepatitis type 1, along with a significant increase in IgG levels. Conclusions: This is the first report of a serological analysis in patients with an IL-12Rβ1 deficiency. Despite the difficulty in interpreting the role of the IL-12, the evidence of liver-specific autoantibodies confirms the importance its signal in liver autoimmunity.

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