Lymphocyte major histocompatibility complex (MHC) class II deficiency also referred to as the bare lymphocyte syndrome, is a rare autosomal recessive primary combined immunodeficiency syndrome that accounts for 5% of all cases of severe combined immunodeficiency and characterized by a defective expression of human leucocyte antigen (HLA) class II molecules due to mutations in four different MHC II regulatory genes (CIITA, RFXANK, RFX5, RFXAP) [
1]. More than 150 patients have been reported worldwide, most of them were originated from North Africa where the frequency of consanguineous marriages is high [
2,
3]. Half of the reported cases have
RFXANK deficiency [
2‐
4]. Clinical manifestations appear early in life including susceptibility to infections, primarily of the respiratory and gastrointestinal tract and severe malabsorption with failure to thrive often leading to death in early childhood [
5,
6]. Supportive treatment includes intravenous immunoglobulin and prophylaxis against
Pneumocystis Jovecci. This therapy results in a marked decrease in the number of bacterial infectious episodes. MHC class II deficiency has a poor prognosis, with a life expectancy of only a few years [
7]. The only curative approach known to date is allogeneic haematopoietic stem cell transplantation [
8]. Few patients survive beyond the age of 20 years under regular immunoglobulin substitution and prophylactic antibiotics. Unknown genetic factors may influence innate or CD8-T cell-mediated immunity, potentially accounting for this more favorable outcome. Genetic predisposition factors and environmental factors such as medical care and family hygiene may be responsible for differences in the clinical expression of the disease state [
9]. Affected patients are extremely susceptible to persistent and recurrent viral infections. The most frequent viral infections include Cytomegalovirus, enterovirus, adenovirus and herpes simplex virus [
4]. MHC class II deficiency patients are at increased risk of oral HPV infection. Negative tuberculin skin test, lymphopenia, and the low CD4+ T cell count indicated that our patients had defects in cellular immunity, which lead to the HPV infection. Genetic factors, malnutrition, and poor hygiene are also found to be associated with this infection. Accompanying features such as growth retardation and poor oral hygiene of our patients might have been facilitating factors. According to other studies [
10,
11], the major histocompatibility complex might contribute to the HPV infection, however HLA typing of our patients revealed an HLA DQB1*0301phenotype. HPV infection has attracted a great deal of attention, not just because of the difficulty of managing oral warts but also because of the oncogenic potential of certain strains [
12]. HPV has been implicated as a cause of several types of benign oral lesions grouped clinically as oral warts. Oral warts can present in almost any location in the mouth as nodular or raised lesions that appear pink or white depending on the degree of keratinization. The majority of these lesions are the result of HPV 6 and 11 [
13]. HPV types 6 and 11 are typically labeled as low risk because infection with these types has low oncogenic potential and usually results in the formation of condylomata and low-grade precancerous lesions. Several treatment options are used to remove oral warts including electro or radiodissecation, laser surgery, cryotherapy, or surgical excision but no treatment is completely satisfactory; relapse is frequent and requires re-treatment [
14]. The lesions of our patients were partially removed by laser surgery.