Oral HPV infection and MHC class II deficiency (A study of two cases with atypical outcome)
© Guirat-Dhouib et al; licensee BioMed Central Ltd. 2012
Received: 22 December 2011
Accepted: 23 April 2012
Published: 23 April 2012
Major histocompatibility complex class II deficiency, also referred to as bare lymphocyte syndrome is a rare primary Immunodeficiency disorder characterized by a profondly deficient human leukocyte antigen class II expression and a lack of cellular and humoral immune responses to foreign antigens. Clinical manifestations include extreme susceptibility to viral, bacterial, and fungal infections. The infections begin in the first year of life and involve usually the respiratory system and the gastrointestinal tract. Severe malabsorption with failure to thrive ensues, often leading to death in early childhood. Bone marrow transplantation is the curative treatment.
Here we report two cases with a late outcome MHC class II deficiency. They had a long term history of recurrent bronchopulmonary and gastrointestinal infections. Bone marrow transplantation could not be performed because no compatible donor had been identified. At the age of 12 years, they developed oral papillomatous lesions related to HPV (human papillomavirus). The diagnosis of HPV infection was done by histological examination. HPV typing performed on the tissue obtained at biopsy showed HPV type 6. The lesions were partially removed after two months of laser treatment.
Viral infections are common in patients with MHC class II and remain the main cause of death. Besides warts caused by HPV infection do not exhibit a propensity for malignant transformation; they can cause great psychosocial morbidity.
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) . 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 . The only curative approach known to date is allogeneic haematopoietic stem cell transplantation . 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 . Affected patients are extremely susceptible to persistent and recurrent viral infections. The most frequent viral infections include Cytomegalovirus, enterovirus, adenovirus and herpes simplex virus . 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 . 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 . 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 . The lesions of our patients were partially removed by laser surgery.
Viral infections are commonly reported in patients with combined immunodeficiency. These reports add to the list of serious infections occurring in association with MHC class II deficiency. Allogeneic hematopoietic stem cell transplantation is the only therapeutic option available for patients with MHC class II deficiency.
The author acknowledges the patients associated with the case studies presented in this manuscript and Emna Lakani for English assistance.
- Siepermann M, Gudowius S, Beltz K, Strier U, Feyen O, Troeger A, Gçbel U, Laws HJ, Kçgler G, Meisel R, Dilloo D, Niehues T: MHC class II deficiency cured by unrelated mismatched umbilical cord blood transplantation: case report and review of 68 cases in the literature. Pediatr Transplantation. 2011, 15: E80-E86. 10.1111/j.1399-3046.2010.01292.x.View ArticleGoogle Scholar
- Reith W, Lisowska-Grospierre B, Fischer A: Molecular basis of major histocompatibility complex class II deficiency. Primary immunodeficiency diseases. Edited by: Ochs HD, Smith CI, Puck JM. New York: Oxford University Press 2007, 227-241.Google Scholar
- Wiszniewski W, Fondaneche MC, Lambert N, Masternak K, Picard C, Notarangelo L, Schwartz K, Bal J, Reith W, Alcaide C, De Saint Basile G, Fischer A, Lisowska-Grospierre B: Founder effect for a 26-bp deletion in the RFXANK gene in North African major histocompatibility complex class II-deficient patients belonging to complementation group B. Immunogenetics. 2000, 51: 261-267. 10.1007/s002510050619View ArticlePubMedGoogle Scholar
- Picard C, Fischer A: Hematopoietic stem cell transplantation and other management strategies for MHC class II deficiency. Immunol Allergy Clin N Am. 2010, 30: 173-178. 10.1016/j.iac.2010.01.001.View ArticleGoogle Scholar
- Griscelli C, Lisowska-Grospierre B, Mach B: Combined immunodeficiency with defective expression of MHC class U genes. Immunodef Rev. 1989, 1: 135-153.PubMedGoogle Scholar
- Villard J, Masternak K, Lisowska-Grospierre B, Fischer A, Reith W: MHC class II deficiency: a disease of gene regulation. Medicine. 2001, 80: 405-418. 10.1097/00005792-200111000-00006View ArticlePubMedGoogle Scholar
- Klein C, Lisowska-Grospierre B, Ledeist F, Fischer A, Griscelli C: Major histocompatibility complex class II deficiency: clinical manifestations, immunological features and outcome. J Pediatr. 1993, 123: 921-928. 10.1016/S0022-3476(05)80388-9View ArticlePubMedGoogle Scholar
- Antoine C, Muller S, Cant A, Cavazzana-Calvo M, Veys P, Vossen J, Fasth A, Heilmann C, Wulffraat N, Seger R, Blanche S, Friedrich W, Abinun M, Davies G, Bredius R, Schulz A, Landais P, Fischer A: Long-term survival and transplantationof haemopoietic stem cells for immunodeficiencies: report of the European experience 1968-99. Lancet. 2003, 361: 553-560. 10.1016/S0140-6736(03)12513-5View ArticlePubMedGoogle Scholar
- Ouederni M, Vincent QB, Frange P, Touzot F, Scerra S, Bejaoui M, Bousfiha A, Levy Y, Lisowska-Grospierre B, Canioni D, Bruneau J, Debré M, Blanche S, Abel L, Casanova JL, Fischer A, Picard C: Major histocompatibility complex class II expression deficiency caused by a RFXANK founder mutation: a survey of 35 patients. Blood. 2011, 118: 5108-5118. 10.1182/blood-2011-05-352716View ArticlePubMedGoogle Scholar
- Spelten B, Grussendorf-Conen EI, Rübben A: Human leukocyte antigen class II alleles and natural history of HPV 2/27/57-induced common warts. Arch Dermatol Res. 2004, 296: 105-111.View ArticlePubMedGoogle Scholar
- Garcia-Corona C, Vega-Memije E, Barquera R, Granados J: HLA-DR alleles associated with skin warts induced by human papillomavirus infection. Inter J Dermatol. 2010, 49: 1376-1379. 10.1111/j.1365-4632.2010.04599.x.View ArticleGoogle Scholar
- Shetty K, Chattopadhyay A, Leigh J: Detection and typing of human papilloma virus in the oral mucosa of patients infected with human immunodeficiency virus. Oral Oncology EXTRA. 2005, 41: 311-315. 10.1016/j.ooe.2005.07.011.View ArticleGoogle Scholar
- Summersgill KF, Smith EM, Levy BT, Allen JM, Haugen TH, Turek LP: Human papillomavirus in the oral cavities of children and adolescents. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001, 91: 62-69. 10.1067/moe.2001.108797View ArticlePubMedGoogle Scholar
- Draganov P, Mateev G, Botev I, Kalvatchev Z: Identification of multiple human papillomavirus (HPV) genotypes in a patient with oral condylomata acuminata. Biotechnol & Biotechnol Eq. 2006, 20: 107-110.View ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.