Abstract
Background
Common variable immunodeficiency (CVID) is defined by hypogammaglobulinemia and increased susceptibility to infections. The gene defect responsible for CVID remains unknown.
Methods
During the course of their CVID disease, a female and three male patients developed microcytic anemia. The investigation of this anemia forms the basis for this report.
Results
Reticulocyte globin chain synthesis studies revealed the abnormal α/β ratios that are pathognomonic of thalassemia. Through transcriptional analysis of the glucose-6-phosphate-dehydrogenase (G6PD) locus of the active X-chromosome in blood cells, we determined that the female patient has clonal reticulocytes, platelets, granulocytes, and B and T lymphocytes.
Conclusions
The simultaneous presence of globin synthesis abnormalities and panhypogammaglobulinemia suggests that a common insult at the stem cell level could contribute to the development of CVID and acquired thalassemia.
Similar content being viewed by others
References
(1992) Primary immunodeficiency diseases: Report of a WHO scientific group. Immunodef. Rev. 3: 195–236.
Volanakis JE, Zhu ZB, Schaffer FM, et al. (1992) Major histocompatibility complex class III genes and susceptibility to immunoglobulin A deficiency and common variable immunodeficiency. J. Clin. Invest. 89: 1914–1922.
Bunn HF, Forget BG. (1986) Hemoglobin: Molecular, Genetic and Clinical Aspects. WB Saunders, Philadelphia.
Anagnou NP, Ley TJ, Chesbro B, et al. (1983) Acquired α-thalassemia in preleukemia is due to decreased expression of all four α-globin genes. Proc. Natl. Acad. Sci. U.S.A. 80: 6051–6055.
Higgs DR, Wood WG, Barton C, Weatherall DJ. (1983) Clinical features and molecular analysis of acquired hemoglobin H disease. Am. J. Med. 69: 181–184.
Hoyle C, Kaeda J, Leslie J, Luzzatto L. (1991) Acquired β thalassemia trait in myelodysplastic syndrome. Brit. J. Med. 79: 116–131.
Prchal JT, Scott CW, Rahbar S, et al. (1989) Mild sickle cell anemia associated with α globin mutant α-Montgomery. Am. J. Med. 75: 232–236.
Prchal JT, Prchal JF, Barany F, Guan YL. (1993) Transcriptional analysis of the active X-chromosome in normal and clonal hematopoiesis. Blood 81: 269–272.
Barany F, Gelfand E. (1991) Cloning over-expression and nucleotide sequence of a thermostable DNA ligase-encoding gene. Gene 109: 1–11.
Prchal JT, Guan YL. (1993) A novel clonality assay based on transcriptional analysis of the active X chromosome. Stem Cells 11: 62–65.
Conley ME, Brown P, Pickard RA. (1986) Expression of the gene defect in X-linked agammaglobulinemia. N. Engl. J. Med. 315: 564–568.
Prchal JT, Carroll AJ, Prchal JF, et al. (1980) Wiscott-Aldrich Syndrome: Cellular impairments and their implication for carrier detection. Blood 56: 1048–1054.
Nyhan WL, Bakay B, Connor JD, Marks JF, Keele DK. (1970) Hemizygous expression of glucose-6-phosphate dehydrogenase in erythrocytes of a heterozygotes for the Lesch-Nyhan syndrome. Proc. Natl. Acad. Sci. USA 65: 214–219.
Felsenfeld G. (1992) Chromatin structure and globin transcription. Nature 355: 219–224.
Peters LL, Andrews NC, Eicher EM, et al. (1993) Mouse microcytic anemia caused by a defect in the gene encoding the globin enhancer-binding protein NF-E2. Nature 1362: 768–770.
Acknowledgments
This work was supported, in part, by a VAH Merit grant (J.T.P.) and United States Public Health Service Grants IRO1 HL51650 and HL50077 (J.T.P.), AR03555 (H.W.S.), AI30879, and AI34568, AR20614 (H.W.S.), AI07051 (S.B.), and AI33621 (H.W.S.). The work was conducted through the General Clinical Research Center of the University of Alabama at Birmingham, supported by USPHS grant MOI RR00032.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Belickova, M., Schroeder, H.W., Guan, Y.L. et al. Clonal Hematopoiesis and Acquired Thalassemia in Common Variable Immunodeficiency. Mol Med 1, 56–61 (1994). https://doi.org/10.1007/BF03403531
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03403531