Protein microarrays identify disease-specific anti-cytokine autoantibody profiles in the landscape of immunodeficiency - 07/01/16
, Jordan V. Price, PhD a, ∗, Gabriela Barcenas-Morales, PhD b, c, ∗, Lourdes Ceron-Gutierrez, BSc, MSc b, Sophie Davies, BSc b, Dinakantha S. Kumararatne, MBBS, FRCpath, DPhil b, Rainer Döffinger, PhD, FRCPath b, d, Paul J. Utz, MD a, e, ⁎ Abstract |
Background |
Anti-cytokine autoantibodies (ACAAs) are pathogenic in a handful of rare immunodeficiencies. However, the prevalence and significance of other ACAAs across immunodeficiencies have not yet been described.
Objective |
We profiled ACAAs in a diverse cohort of serum samples from patients with immunodeficiency and assessed the sensitivity and specificity of protein microarrays for ACAA identification and discovery.
Methods |
Highly multiplexed protein microarrays were designed and fabricated. Blinded serum samples from a cohort of 58 immunodeficiency patients and healthy control subjects were used to probe microarrays. Unsupervised hierarchical clustering was used to identify clusters of reactivity, and after unblinding, significance analysis of microarrays was used to identify disease-specific autoantibodies. A bead-based assay was used to validate protein microarray results. Blocking activity of serum containing ACAAs was measured in vitro.
Results |
Protein microarrays were highly sensitive and specific for the detection of ACAAs in patients with autoimmune polyendocrine syndrome type I and pulmonary alveolar proteinosis, detecting ACAA levels consistent with those reported in the published literature. Protein microarray results were validated by using an independent bead-based assay. To confirm the functional significance of these ACAAs, we tested and confirmed the blocking activity of select ACAAs in vitro.
Conclusion |
Protein microarrays are a powerful tool for ACAA detection and discovery, and they hold promise as a diagnostic for the evaluation and monitoring of clinical immunodeficiency.
Le texte complet de cet article est disponible en PDF.Key words : Anti-cytokine autoantibodies, immunodeficiency, autoimmune polyendocrine syndrome type I, pulmonary alveolar proteinosis, thymoma, protein microarray
Abbreviations used : ACAA, AIRE, APS-1, MFI, MIP-1α, PAP, PBST, SAM
Plan
| Research reported in this publication was supported by the National Institutes of Health (NIH) under award number T32GM007365. P.J.U. is the recipient of a Donald E. and Delia B. Baxter Foundation Career Development Award, a gift from the Floren Family Trust, and a gift from the Ben May Charitable Trust (Mobile, Alabama) and is supported by National Heart, Lung, and Blood Institute (NHLBI) Proteomics contract N01-HV-00242, HSN268201000034C, NIH grants (1 U19-AI110491, 1 U19-AI090019, 1 UH2 AR067676, 1 UM2 AR067678, and 1 UM1AI110498), the Alliance for Lupus Research (grant no. 21858), and FP grant no. 261. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 261382. G.B.-M. was supported by grants from UNAM-DGAPA-PAPIIT (grants IN217312-3 and IN220815). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. |
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| Disclosure of potential conflict of interest: D. S. Kumararatne has received grants from the National Institute for Health Research Cambridge Biomedical Centre, has received payment for lectures from Baxter, and has received travel support from CSL Behring and Shire. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 137 - N° 1
P. 204 - janvier 2016 Retour au numéro
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