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

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:

• Primary Immunodeficiency
• autoimmune lymphoproliferative syndrome
• ALPS
• lymphoproliferation
• autoimmunity
• PRKCD

Conflicts of Interest

The authors declare that they have no conflict of interest.

Additional information

Funding

This work was supported by the vice chancellor for research, Alborz University of Medical Sciences [1397-03-25-1951].