Immundeficiency 35

Immunodeficiency 35 is a rare, autosomal recessive primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and severely elevated serum IgE. It is considered a variant of the hyper-IgE syndrome and is caused by a mutation in the TYK2 gene .

Minegishi et al (2006) described a 22-year-old Japanese man who was clinically diagnosed with autosomal recessive hyper IgE syndrome (HIES), a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and severely elevated serum IgE. The patient had a history of susceptibility to various microorganisms, including viruses, fungi, and mycobacteria. He had an episode of Bacille Calmette-Guerin (BCG) infection at 22 months of age and non-Typhi salmonella gastroenteritis at 15 years of age.

Woellner et al. (2007) noted that the patient with TYK2 deficiency reported by Minegishi et al. (2006) had clinical features atypical of autosomal recessive HIES, including BCG lymphadenitis and nontyphic Salmonella infection.

Kilic et al (2012) reported a Turkish boy from consanguineous parents who presented in infancy with disseminated BCG infection. Laboratory tests showed a slightly elevated serum IgE. At age 8, he developed neurobrucellosis with permanent neurologic sequelae, followed by herpes zoster at age 11. He had no evidence of atopy, no asthma, and no fungal infections of the skin or mucous membranes. Kilic et al. (2012) noted that the phenotype in this patient overlapped with but differed slightly from that reported by Minegishi et al. (2006).

Kreins et al (2015) reported 6 patients from 4 unrelated families with IMD35. The patients were from different countries, including Morocco, Iran, and Argentina. All received BCG vaccination, and responded with systemic reactions to it. One patient presented with disseminated extrapulmonary tuberculosis at 13 years of age after being vaccinated at birth. Others developed localized BCG lymphadenopathy after vaccination in infancy. One patient never had an adverse reaction to BCG vaccination but had disseminated cutaneous herpetic lesions associated with aseptic herpes meningitis. Another patient had recurrent otitis and urinary tract infections, as well as asthma and eczema, but was alive at age 15 years. None of the patients had documented pyogenic infections, including staphylococcal infections, or fungal infections, including mucocutaneous candidiasis.

1. Kilic S S et al.(2012) A patient with tyrosine kinase 2 deficiency without hyper-IgE syndrome. J Pediat. 160: 1055-1057
2. Krein AY et al.(2015) Human TYK2 deficiency: mycobacterial and viral infections without hyper-IgE syndrome. J. Exp. Med 1641-1662.
3. Minegishi, Y., Saito, M., Karasuyama, H. Response: the hyper IgE syndrome and mutations in TYK2. (Letter) Immunity 226: 536 only, 2007.
4. Minegishi Y et al.(2006) Human tyrosine kinase 2 deficiency reveals its requisite roles in multiple cytokine signals involved in innate and acquired immunity. Immunity 25: 745-755
5. Woellner C et al.(2007) The hyper IgE syndrome and mutations in TYK2. (Letter) Immunity 26: 535.