Protein Kinase C-Delta Defect in Autoimmune Lymphoproliferative Syndrome-Like Disease: First Case from the National Iranian Registry and Review of the Literature

Immunol Invest. 2022 Feb;51(2):331-342. doi: 10.1080/08820139.2020.1829638. Epub 2020 Oct 13.

Abstract

Background: Protein kinase C is a family of serine/threonine kinases that play a key role in the adaptive immune cell signaling, as well as regulation of growth, apoptosis, and differentiation of a variety of cell types. Patients homozygous for a null mutation of the Protein Kinase C Delta (PRKCD) gene, present clinical feature of immune dysregulation with susceptibility to Epstein-Barr virus infection. However, a minority of patients present the autoimmune lymphoproliferative syndrome (ALPS).

Methods: The data were collected by direct interview and examining the patient's clinical record. Whole-exome sequencing was performed to detect the underlying genetic mutation in the patient. We also conducted electronic searches for ALPS-like reported patients in PubMed, Web of Science, and Scopus databases.

Results: In this study, we reported a 13-year-old boy who presented with autoimmunity, lymphoproliferation, recurrent pneumonia, cardiomyopathy, and dermatological manifestations. An elevation of double-negative T cells, CD8+ T cells, serum IgG level, as well as a reduction in NK cells, was observed in the patient. A homozygous frameshift mutation (c.1293_1294insA) in exon 13 of the PRKCD gene was confirmed. The literature search showed 39 ALPS-like patients with monogenic defects which only six (15.3%) of them were due to PRKCD genes.

Conclusion: PRKCD should be considered in the context of ALPS clinical manifestations with prominent dermatological involvements.

Keywords: ALPS; PRKCD; Primary Immunodeficiency; autoimmune lymphoproliferative syndrome; autoimmunity; lymphoproliferation.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adolescent
  • Autoimmune Diseases*
  • Autoimmune Lymphoproliferative Syndrome* / diagnosis
  • Autoimmune Lymphoproliferative Syndrome* / genetics
  • CD8-Positive T-Lymphocytes
  • Epstein-Barr Virus Infections*
  • Herpesvirus 4, Human
  • Humans
  • Iran
  • Male
  • Mutation
  • Protein Kinase C-delta
  • Registries

Substances

  • Protein Kinase C-delta