Page 506 - Clinical Immunology_ Principles and Practice ( PDFDrive )
P. 506
486 PARt fouR Immunological Deficiencies
hypogammaglobulinemia syndrome complex that includes CVID 4. De Greef GE, van Tol MJ, Van Den Berg JW, et al. Serum
and may ultimately require long-term therapy with gamma- immunoglobulin class and IgG subclass levels and the occurrence of
globulin, prophylactic antibiotics, or both. homogeneous immunoglobulins during the course of ageing in humans.
Mech Ageing Dev 1992;66:29–44.
Treatment and Prognosis 5. Stiehm ER, Fudenberg HH. Serum levels of immune globulins in health
and disease: a survey. Pediatrics 1966;37:715–27.
Children with suspected THI should be monitored with serial 6. Soothill JF, Hayward AR, Wood CB. Pediatric immunology. Oxford, UK:
determination of serum Igs and isohemagglutinin titers to confirm Blackwell Scientific Publications; 1983:463–4.
acquisition of normal immune function. Some children will not 7. Gharib A, Caperton C, Gupta S. Anaphylaxis to IGIV in
achieve normal levels of IgG for several years, and some will immunoglobulin-naive common variable immunodeficiency patient in
remain IgG subclass or IgA deficient. Treatment of THI with the absence of IgG anti-IgA antibodies: successful administration of low
IVIG is generally not warranted unless the child suffers from IgA-containing immunoglobulin. Allergy Asthma Clin Immunol
persistent, recurrent, invasive infections, including pneumonia. 2016;12:23.
8. Carr TF, Koterba AP, Chandra R, et al. Characterization of specific
antibody deficiency in adults with medically refractory chronic
oN tHE HoRIZoN rhinosinusitis. Am J Rhinol Allergy 2011;25:241–4.
9. Lopez-Herrera G, Vargas-Hernandez A, Gonzalez-Serrano ME, et al.
• Elucidation of the molecular basis of selective defects in humoral Bruton’s tyrosine kinase—an integral protein of B cell development that
responses to pathogens, in part through the use of high-throughput also has an essential role in the innate immune system. J Leukoc Biol
sequencing to characterize the precise molecular composition of 2014;95:243–50.
antibody responses in immune deficiencies 10. Nelson KS, Lewis DB. Adult-onset presentations of genetic
• Further elucidation of the molecular basis of common variable immune immunodeficiencies: genes can throw slow curves. Curr Opin Infect Dis
deficiency, hypogammaglobulinemia, and immunoglobulin A (IgA) 2010;23:359–64.
deficiency
11. Sigmon JR, Kasasbeh E, Krishnaswamy G. X-linked agammaglobulinemia
diagnosed late in life: case report and review of the literature. Clin Mol
Allergy 2008;6:5.
FRONTIERS IN RESEARCH 12. Stewart DM, Tian L, Notarangelo LD, et al. X-linked
hypogammaglobulinemia and isolated growth hormone deficiency: an
Bruton reported the first case of agammaglobulinemia in 1952, update. Immunol Res 2008;40:262–70.
as well as the first successful therapy for this classic primary 13. Winkelstein JA, Conley ME, James C, et al. Adults with X-linked
antibody deficiency. There has been remarkable progress in the agammaglobulinemia: impact of disease on daily lives, quality of life,
identification of single-gene disorders since that time. However, educational and socioeconomic status, knowledge of inheritance, and
for the majority of patients the underlying pathogenesis of the reproductive attitudes. Medicine (Baltimore) 2008;87:253–8.
most common manifestation of primary antibody deficiency in 14. Conley ME, Dobbs AK, Farmer DM, et al. Primary B cell
our population, that is, hypogammaglobulinemia in the adult, immunodeficiencies: comparisons and contrasts. Annu Rev Immunol
still remains unclear. It seems increasingly likely that this disorder 2009;27:199–227.
is multifactorial in nature, dependent on the inheritance of one 15. Boisson B, Wang YD, Bosompem A, et al. A recurrent dominant negative
or more susceptibility loci in association with either environmental E47 mutation causes agammaglobulinemia and BCR(−) B cells. J Clin
Invest 2013;123:4781–5.
influences or random chance. In rare cases, patients with hypo- 16. Sawada A, Takihara Y, Kim JY, et al. A congenital mutation of the novel
gammaglobulinemia have shown resolution of their symptoms, gene LRRC8 causes agammaglobulinemia in humans. J Clin Invest
suggesting that a better understanding of pathogenesis might 2003;112:1707–13.
yield therapies of remission. The molecular basis of selective 17. Conley ME, Dobbs AK, Quintana AM, et al. Agammaglobulinemia and
deficiencies in the response to pathogens in the presence of absent B lineage cells in a patient lacking the p85alpha subunit of PI3K.
normal serum Ig levels also remains unclear. The availability of J Exp Med 2012;209:463–70.
whole exome sequencing and whole-genome sequencing has 18. Durandy A, Kracker S. Immunoglobulin class-switch recombination
helped identify the genetic cause of an increasing number of deficiencies. Arthritis Res Ther 2012;14:218.
patients with presumed CVID. More genes and likely presumptive 19. Karaca NE, Durandy A, Gulez N, et al. Study of patients with Hyper-IgM
alleles will be found in the next decade. type IV phenotype who recovered spontaneously during late childhood
and review of the literature. Eur J Pediatr 2011;170:1039–47.
20. Kawai T, Nishikomori R, Heike T. Diagnosis and treatment in anhidrotic
Please check your eBook at https://expertconsult.inkling.com/ ectodermal dysplasia with immunodeficiency. Allergol Int 2012;61:207–17.
for self-assessment questions. See inside cover for registration 21. Hennig C, Baumann U, Ilginus C, et al. Successful treatment of
details. autoimmune and lymphoproliferative complications of patients with
intrinsic B-cell immunodeficiencies with Rituximab. Br J Haematol
REFERENCES 2010;148:445–8.
22. Schroeder HW Jr, Schroeder HW III, Sheikh SM. The complex genetics of
1. Durandy A, Kracker S, Fischer A. Primary antibody deficiencies. Nat Rev common variable immunodeficiency. J Investig Med 2004;52:90–103.
Immunol 2013;13:519–33. 23. Johnston DT, Mehaffey G, Thomas J, et al. Increased frequency of HLA
2. Johnson ML, Keeton LG, Zhu ZB, et al. Age-related changes in serum -B44 in Recurrent Sino-Pulmonary Infections (RESPI). Clin Immunol
immunoglobulins in patients with familial IgA deficiency and common 2006;119:346–50.
variable immunodeficiency (CVID). Clin Exper Immunol 24. Nielsen LK, Dziegiel MH. Recombinant human immunoglobulin (Ig)A1
1997;108:477–83. and IgA2 anti-D used for detection of IgA deficiency and anti-IgA.
3. Litzman J, Freiberger T, Grimbacher B, et al. Mannose-binding lectin gene Transfusion 2008;48:1892–7.
polymorphic variants predispose to the development of 25. Borrelli M, Maglio M, Agnese M, et al. High density of intraepithelial
bronchopulmonary complications but have no influence on other clinical gammadelta lymphocytes and deposits of immunoglobulin (Ig)M
and laboratory symptoms or signs of common variable anti-tissue transglutaminase antibodies in the jejunum of coeliac patients
immunodeficiency. Clin Exper Immunol 2008;153:324–30. with IgA deficiency. Clin Exper Immunol 2010;160:199–206.

