Evaluation of autoantibody signatures in pituitary adenoma patients using human proteome arrays

Proteomics Clin Appl. 2022 Nov;16(6):e2100111. doi: 10.1002/prca.202100111. Epub 2022 Sep 18.

Abstract

Purpose: To identify the specific diagnostic biomarkers related to pituitary adenomas (PAs), we performed serological antibody profiles for three types of PAs, namely Acromegaly, Cushing's and Nonfunctional Pituitary Adenomas (NFPAs), using the human proteome (HuProt) microarray. This is the first study describing the serum autoantibody profile of PAs.

Experimental design: We performed serological autoantibody profiling of four healthy controls, four Acromegaly, three Cushing's and three NFPAs patient samples to obtain their autoantibody profiles, which were used for studying expression, interaction and altered biological pathways. Further, significant autoantibodies of PAs were compared with data available for glioma, meningioma and AAgAtlas for their specificity.

Results: Autoantibody profile of PAs led to the identification of differentially expressed significant proteins such as AKNAD1 (AT-Hook Transcription Factor [AKNA] Domain Containing 1), NINJ1 (Nerve injury-induced protein 1), L3HYPDH (Trans-3-hydroxy-L-proline dehydratase), RHOG (Rho-related GTP-binding protein) and PTP4A1 (Protein Tyrosine Phosphatase Type IVA 1) in Acromegaly. Protein ABR (Active breakpoint cluster region-related protein), ST6GALNAC6 (ST6 N-acetylgalactosaminide alpha-2, 6-sialyltransferase 6), NOL3 (Nucleolar protein 3), ANXA8 (Annexin A8) and POLR2H (RNA polymerase II, I and III subunit H) showed an antigenic response in Cushing's patient's serum samples. Protein dipeptidyl peptidase 3 (DPP3) and reticulon-4 (RTN4) exhibited a very high antigenic response in NFPA patients. These proteins hold promise as potential autoantibody biomarkers in PAs.

Keywords: acromegaly; auto antibody; cushing's and nonfunctional adenomas; multiple reaction monitoring; pituitary adenomas; protein microarray.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acromegaly*
  • Adenoma* / genetics
  • Autoantibodies
  • Cell Adhesion Molecules, Neuronal
  • DNA-Binding Proteins
  • Humans
  • Nerve Growth Factors
  • Nuclear Proteins
  • Pituitary Neoplasms* / genetics
  • Proteome
  • Transcription Factors

Substances

  • Proteome
  • Autoantibodies
  • AKNA protein, human
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Transcription Factors
  • NINJ1 protein, human
  • Nerve Growth Factors
  • Cell Adhesion Molecules, Neuronal