FaCD Online Syndrome Fact Sheet

Last updated: 10 Mar 2008

Name: IgA Deficiency, Selective

Synonym: IGAD1, IGAD2

Mode of Inheritance: AD?/ multifact?

Genes

IGAD1, mapped to 6p21.3
TNFRSF13B, mapped to 17p11.2

Tumor features

gastric cancer

Tumor features (possible)

breast cancer
choroidal tumor
colorectal cancer
esophageal cancer
Hodgkin disease (Hodgkin's lymphoma)
leukemia
lung/bronchial cancer
non-Hodgkin lymphoma
ovarian cancer (i.e. epithelial origin)
skin cancer, squamous cell
thymoma

Non-tumor features

IgA deficiency, selective
immunodeficiency

Comment

This is the most common type of immunodeficiency, characterized by a selective defect in IgA production. The origin is probably heterogeneous and the disorder is associated with other conditions, celiac disease is the most frequent of those.[16].

There appears to be an increased risk to develop gastric adenocarcinoma in patients with this disorder[1;2] and possibly there is an increased risk to develop Hodgkin disease and Non-Hodgkin lymphoma as well[2-4,15]. In a review by Filopovich et al.[4], approximately 8 % of IgA deficiency patients were reported to have developed a tumor. In a cohort of cancer patients, selective IgA deficiency has been detected in a higher frequency than in the general population, especially in the patients with lymphoproliferative disease and gastrointestinal cancer[5].

Schuelke et al.[6] reported on a family with multiple cases of ovarian cancer segregating with low serum IgA levels. Abdominal wall fibrosarcoma in a 17-year-old girl with IgA deficiency was reported by Verkasalo et al.[7]. Kuhn[8] reported on a 45 year old woman with a selective IgA deficiency and alcohol and tobacco abuse, who developed oral cancer. A range of other tumors has been reported as well[9-12].
Hamoudi et al.[13] reported a girl who developed multiple adenomatous polyps in her colon (1 malignant) at the age of 10, after which she developed over a period of 8 years a malignant thymoma, squamous cell cancer of the scalp, colon cancer, choroidal tumor, finally dying at the age of 20 from a brain tumor (astrocytoma). She had low Ig A and IgG2 levels, normal IgM and total IgG. Her brother had a total absence of IgA, low IgG and high IgM and died at the age of 16 from a lymphocytic lymphoma. Although this family was reported with an emphasis on the IgA deficiency, there is no selective IgA deficiency (possibly a variant of Hyper-IgM syndrome? Epstein-Barr virus infections may play a role in tumor development in patients with IgA deficiency[14]

Links

International Patient Organisation for Primary Immunodeficiencies (IPOPI) 18 1 08

References

[1] Gatti RA, Good RA. Occurrence of malignancy in immunodeficiency diseases. A literature review. Cancer 1971; 28(1):89-98.
[2] Filipovich AH, Spector BD, Kersey J. Immunodeficiency in humans as a risk factor in the development of malignancy. Prev Med 1980; 9:252-259.
[3] Zenone T, Souquet PJ, Cunningham-Rundles C, Bernard JP. Hodgkin's disease associated with IgA and IgG subclass deficiency. J Int Med 1996; 240(2):99-102.
[4] Filipovich AH, Mathur A, Kamat D, Kersey JH, Shapiro RS. Lymphoproliferative disorders and other tumors complicating immunodeficiencies. Immunodeficiency 1994; 5(2):91-112.
[5] Cunningham-Rundles C, Pudifin DJ, Armstrong D, Good RA. Selective IgA deficiency and neoplasia. Vox Sang 1980; 38(2):61-67.
[6] Schuelke GS, Lynch HT, Lynch JF, Fain PR, Chaperon EA. Low serum IgA in a familial ovarian cancer aggregate. Cancer Genet Cytogenet 1982; 6(3):231-236.
[7] Verkasalo M, Savilahti E, Rapola J, Wallgren EI. Fibrosarcoma in a girl with celiac disease and IgA deficiency. J Pediatr Gastroenterol Nutr 1985; 4(5):839-841.
[8] Kuhn A. [Ulcerative dermatitis (pyoderma gangrenosum) with selective IgA deficiency and development of an oral carcinoma]. Z Hautkr 1985; 60(1-2):79-82.
[9] Goh KO, Reddy MM, Webb DR. Cancer in a familial IgA deficiency patient: abnormal chromosomes and B lymphocytes. Oncology 1976; 33(5-6):237-240.
[10] Kersey JH, Spector BD, Good RA. Primary immunodeficiency diseases and cancer: the immunodeficiency-cancer registry. Int J Cancer 1973; 12(2):333-347.
[11] Spector BD, Perry GS, Kersey JH. Genetically determined immunodeficiency diseases (GDID) and malignancy: report from the immunodefciency-cancer registry. Clin Immunol Immunopathol 1978; 11:12-29.
[12] Hayakawa H, Kobayashi N, Yata J. Primary immunodeficiency diseases and malignancy in Japan. Jpn J Cancer Res 1986; 77(1):74-79.
[13] Hamoudi AB, Ertel I, Newton WA, Jr., Reiner CB, Clatworthy HW, Jr. Multiple neoplasms in an adolescent child associated with IGA deficiency. Cancer 1974; 33(4):1134-1144.
[14] Purtilo DT, Liao SA, Sakamoto K, Snyder LM, DeFlorio D, Jr., Bhawan J, Paquin L, Yang JP, Hutt-Fletcher LM, Muralidharan K, Raffa P, Saemundsen AK, Klein G. Diverse familial malignant tumors and Epstein-Barr virus. Cancer Res 1981; 41(11 Pt 1):4248-4252.
[15] Ott MM, Ott G, Klinker H, Trunk MJ, Katzenberger T, Müller-Hermelink HK. Abdominal T-cell non-Hodgkin's lymphoma of the gamma/delta type in a patient with selective immunoglobulin A deficiency. The American journal of surgical pathology 1998; 22(4):500-6.
[16] Latiff AH, Kerr MA. The clinical significance of immunoglobulin A deficiency. Annals of clinical biochemistry 2007; 44(Pt 2):131-9.