Graft Versus Host Disease and Microchimerism in a Jak3 Deficient Patient Publisher



Shahbazi Z¹ ; Parvaneh N² ; Shahbazi S³ ; Rahimi H¹ ; Hamid M¹ ; Shahbazi D⁴ ; Delavari S² ; Abolhassani H^{2, 5} ; Aghamohammadi A^{2, 6} ; Mahdian R¹ Show Affiliations
Source: Allergy# Asthma and Clinical Immunology Published:2019

Abstract

Background: The lymphohematopoietic cells originating from feto-maternal trafficking during pregnancy may cause microchimerism and lead to materno-fetal graft versus host disease (GVHD) in severe combined immunodeficiency (SCID) patients. However, definitive diagnosis between GVHD and Omenn's syndrome is often difficult based on clinical and immunological phenotypes particularly in the patients with hypomorphic mutations. Case presentation: A 3-year-old girl with a history of erythroderma and immunodeficiency was studied. The whole exome sequencing method was used to find the disease-causing variants, and T-A cloning and Quantitative Florescence Polymerase Chain Reaction (QF-PCR) methods were utilized to detect the presence of mosaicism or microchimerism. We identified a homozygous missense Janus Kinase 3 mutation (JAK3, c.2324G>A, p.R775H) as a new disease-causing variant in the patient, and the presence of microchimerism with maternal origin was proven as an underlying cause of her clinical presentation. Conclusion: The findings highlighted the importance of appropriate diagnostic approach in GVHD cases with hypomorphic JAK3 mutations. When analyzing the results of the next generation sequencing, the possibility of microchimerism should be considered based on the context of the disease. © 2019 The Author(s).