MHC Class II Deficiency with Normal CD4+ T Cell Counts: A Case Report
AbstractMajor histocompatibility complex (MHC) class II deficiency is a rare primary immunodeficiency disorder (PID) with less than 200 cases worldwide. Here, we report an 8 month–old girl with MHC class II deficiency with a novel homozygous mutation in RFXANK gene (NM_001278728: exon 5: c.495G>A: p.Trp165*) and normal CD4+ T cell counts, diagnosed by whole exome sequencing (WES) and negative HLA–DR proteins on peripheral blood mononuclear cell (PBMC) in flow cytometry. She was referred with pneumonia, prolonged fever, resistance to antibiotics (ceftriaxone, clindamycin, and vancomycin), and low serum immunoglobulin (IG) levels, while natural killer (NK), B, and T cells were normal. She received intra-venous immune-globulin (IVIG) replacement, broad spectrum antibiotics, and anti-fungal treatments. The presented case report is interesting not only because of the rarity of the PID but also due to normal CD4+ T cell counts. According to our experience, we suggest that physicians consider MHC class II deficiency in families with consanguineous marriages, even with normal CD4+ T cell counts. At the first, the diagnosis of the disease could be successfully perform using WES, and finally, treatment with hematopoietic stem cell transplantation can save the patients’ lives.
1. Serrano-Martín M, Moreno-Perez D, García-Martín F, Jurado-Ortiz A, editors. Major histocompatibility complex class II deficiency. Anales de pediatria (Barcelona, Spain: 2003); 2007.2. Ben-Mustapha I, Ben-Farhat K, Guirat-Dhouib N, Dhemaied E, Largueche B, Ben-Ali M, et al. Clinical, immunological and genetic findings of a large tunisian series of major histocompatibility complex class II deficiency patients. Journal of clinical immunology. 2013;33(4):865-70.3. Al-Mousa H, Al-Saud B. Primary immunodeficiency Diseases in Highly Consanguineous Populations from Middle east and north Africa: epidemiology, Diagnosis, and Care. Frontiers in immunology. 2017;8.4. Saleem M, Arkwright P, Davies E, Cant A, Veys P. Clinical course of patients with major histocompatibility complex class II deficiency. Archives of disease in childhood. 2000;83(4):356-9.5. Villard J, Masternak K, Lisowska-Grospierre B, Fischer A, Reith W. MHC class II deficiency: a disease of gene regulation. Medicine. 2001;80(6):405-18.6. Ouederni M, Vincent QB, Frange P, Touzot F, Scerra S, Bejaoui M, et al. Major histocompatibility complex class II expression deficiency caused by a RFXANK founder mutation: a survey of 35 patients. Blood. 2011;118(19):5108-18.7. Naamane H, El Maataoui O, Ailal F, Barakat A, Bennani S, Najib J, et al. The 752delG26 mutation in the RFXANK gene associated with major histocompatibility complex class II deficiency: evidence for a founder effect in the Moroccan population. European journal of pediatrics. 2010;169(9):1069-74.8. Djidjik R, Messaoudani N, Tahiat A, Meddour Y, Chaib S, Atek A, et al. Clinical, immunological and genetic features in eleven Algerian patients with major histocompatibility complex class II expression deficiency. Allergy, Asthma & Clinical Immunology. 2012;8(1):14.9. Alyasin S, Abolnezhadian F, Khoshkhui M. A Case of Probable MHC Class II Deficiency with Disseminated BCGitis. Iranian journal of immunology : IJI. 2015;12(3):219-25.10. Parvaneh N, Shahmahmoudi S, Tabatabai H, Zahraei M, Mousavi T, Esteghamati AR, et al. Vaccine-associated paralytic poliomyelitis in a patient with MHC class II deficiency. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 2007;39(2):145-8.11. Farrokhi S, Shabani M, Aryan Z, Zoghi S, Krolo A, Boztug K, et al. MHC class II deficiency: Report of a novel mutation and special review. Allergologia et immunopathologia. 2017.12. Bensinger SJ, Bandeira A, Jordan MS, Caton AJ, Laufer TM. Major histocompatibility complex class II–positive cortical epithelium mediates the selection of CD4+ 25+ immunoregulatory T cells. Journal of Experimental Medicine. 2001;194(4):427-38.13. Ben-Mustapha I, Ben-Farhat K, Guirat-Dhouib N, Dhemaied E, Larguèche B, Ben-Ali M, et al. Clinical, immunological and genetic findings of a large Tunisian series of major histocompatibility complex class II deficiency patients. Journal of clinical immunology. 2013;33(4):865-70.14. Saadat M, Ansari-Lari M, Farhud D. Short report consanguineous marriage in Iran. Annals of human biology. 2004;31(2):263-9.15. Saadat M. Consanguineous marriages in Iranian folktales. Public Health Genomics. 2007;10(1):38-40.16. Antoine C, Müller S, Cant A, Cavazzana-Calvo M, Veys P, Vossen J, et al. Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: report of the European experience 1968–99. The Lancet. 2003;361(9357):553-60.17. Renella R, Picard C, Neven B, Ouachée‐Chardin M, Casanova JL, Deist FL, et al. Human leucocyte antigen‐identical haematopoietic stem cell transplantation in major histocompatiblity complex class II immunodeficiency: reduced survival correlates with an increased incidence of acute graft‐versus‐host disease and pre‐existing viral infections. British journal of haematology. 2006;134(5):510-6.18. Al-Mousa H, Al-Shammari Z, Al-Ghonaium A, Al-Dhekri H, Al-Muhsen S, Al-Saud B, et al. Allogeneic stem cell transplantation using myeloablative and reduced-intensity conditioning in patients with major histocompatibility complex class II deficiency. Biology of Blood and Marrow Transplantation. 2010;16(6):818-23.19. Klein C, Cavazzana-Calvo M, Le Deist F, Jabado N, Benkerrou M, Blanche S, et al. Bone marrow transplantation in major histocompatibility complex class II deficiency: a single-center study of 19 patients. Blood. 1995;85(2):580-7.