One hundred and twenty-four patients (from 120 families) diagnosed as primary immunodeficiency diseases were enrolled from five tertiary medical centers. The distribution by an update eight categories showed 45 patients (13 females/32 males; 36.3%) with “predominant antibody deficiencies,” 27 patients (6/21; 21.8%) with “T- and B-cell immunodeficiency,” 25 patients (9/16; 20.2%) with “congenital defects of phagocyte,” 25 patients (4/21; 20.2%) with “other well-defined immunodeficiency syndromes,” one boy (0.8%) with “disease in immune deregulation” (Chediak-Higashi syndrome) and another with “complement 3 deficiency.” None had “defects in innate immunity” or “auto inflammatory disorders.” Pseudomonas and Salmonella spp. were the two most identified microorganisms in septicemia (39.7%; 27/68 episodes). Twenty-three patients (18.5%) had mortality. Stem cell transplantation succeeded in 7 of 12 patients. In addition to nine patients with DiGerge syndrome recognized by FISH, direct sequencing identified 12 unique mutations from 20 families, reflecting distinct Taiwan geography, although a selection bias may exist.
Similar content being viewed by others
Abbreviations
- PIDs:
-
primary immunodeficiency diseases
- HIGM:
-
hyper IgM syndrome
- NEMO:
-
nuclear factor kB (NF-κB) essential modulator
- ICOS:
-
inducible co-stimulatory molecule
- ICOSL:
-
ICOS ligand
- CVID:
-
common variable immunodeficiency
- CD40L:
-
CD40 ligand
- AID:
-
activation-induced cytidine deaminase
- SAP:
-
signaling lymphocyte activation molecule-associated protein
- WASP:
-
Wiskott-Aldrich syndrome protein
- AT:
-
ataxia telangiectasia
- HIES:
-
hyper IgE syndrome
- LAD:
-
leukocyte adhesion disease
- CHS:
-
Chediak-Higashi syndrome
- SCID:
-
severe combined T- and B-cell immunodeficiency
- CGD:
-
chronic granulomatous disease
- GvHD:
-
graft vs. host disease
- PBMC:
-
peripheral blood mononuclear cells
- RT-PCR:
-
reverse transcriptase polymerase chain reaction
- FISH:
-
fluorescence in situ hybridization.
REFERENCES
Smith CIE, Ochs HD, Puck JM: Genetically determined immunodeficiency diseases: A perspective. In Primary Immunodeficiency Diseases, HD Ochs, CIE Smith, JM Puck (eds). New York, Oxford, 1999, pp 3–11
Bruton OC: Agammaglobulinemia. Pediatrics 9:772–778, 1952
Stiehm ER, Ochs HD, Winkelstein JA: Immunologic disorders: General considerations. In Immunodeficiency Disorders in Infants and Children, ER Stiehm, HD Ochs, JA Winkelstein (eds). Philadelphia, WB Saunders, 2004, pp 289–355
Notarangelo L, Casanova JL, Fischer A, Puck J, Rosen F, Seger R: Primary immunodeficiency diseases: An update. J Allergy Clin Immunol 114:677–687, 2004
Lee WI, Kuo ML, Huang JL, Lin SJ, Wu CJ: Distribution and clinical aspects of primary immunodeficiencies in a Taiwan Pediatric tertiary hospital during a 20-year-period. J Clin Immunol 25:162–173, 2005
Yang YL, Lu MY, Jou ST, Lin KH, Lin DT: Hematopoietic stem cell transplantation in Taiwanese children with primary immunodeficiency. J Formos Med Assoc 104:101–106, 2005
Weng JD, Shyur SD: X-linked chronic granulomatous disease: Report of one case. Acta Paediatr Tw 45:163–167, 2004
Hung CH, Cheng SN, Hua YM, Wang CL, Chen YH, Yang KD: Leukocyte adesion deficiency disorder: Report of one case. Acta Paediatr Sin 40:128–131, 1999
Chien YH, Hwu WL, Ariga T, Chang KW, Yang YH, Lin KH, Chiang BL: Molecular diagnosis of Wiskott-Aldrich syndrome in Taiwan. J Microbiol Immunol Infect 37:276–281, 2004
Lin SC, Shyur SD, Ma YC, Huang LH, Lee WI: Hyper-IgM1 syndrome with interstitial pneumonia and diarrhea caused by coxsackievirus B4 in a 3-month-old infant. Ann Allergy Asthma Immunol 95:93–97, 2005
Ma YC, Lee WI, Lin SC, Huang LH, Wu JY: De novo mutation causing X-linked hyper-IgM syndrome: A family study in Taiwan. Asian Pac J Allergy Immunol 23:53–59, 2005
Lin SJ, Huang YF, Chen JY, Heyworth PG, Noack D, Wang JY, Lin CY, Chiang BL, Yang CM, Liu CC, Shieh CC: Molecular quality control machinery contributes to the leukocyte NADPH oxidase deficiency in chronic granulomatous disease. Biochim Biophys Acta 1586:275–286, 2002
Wang LH, Tsai MJ, Huang MT, Lin SC, Chiang BL: Autoimmune manifestations in patients with primary immunodeficiency. Acta Paediatr Tw 40:243–249, 1999
Wang LJ, Yang YH, Lin YT, Chiang BL: Immunological and clinical features of pediatric patients with primaty hypogammaglobulinemia in Taiwan. Asian Pac J Allergy Immunol 22:25–31, 2004
Hung CH, Hua YM, Huang CF, Luo WT, Yang KD, Chu ML, Wang CC: Chronic granulomatous disease: A case report. J Formos Med Assoc 100:281–284, 2001
Lee WI, Torgerson TR, Schumacher MJ, Yel L, Zhu Q, Ochs HD: Mutation analysis in a large cohort patients with hyper IgM syndrome. Blood 105:1881–1890, 2005
Lee WI, Zhu Q, Gambineri E, Jin Y, Welcher AA, Ochs HD: Inducible CO-Stimulator molecule (ICOS), a candidate gene for defective isotype switching, is normal in patients with Hyper IgM syndrome of unknown molecular diagnosis. J Allergy Clin Immunol 112:958–964, 2003
Driscoll DA, Salvin J, Sellinger B, Budarf ML, McDonald-McGinn DM, Zackai EH, Emanuel BS: Prevalence of 22q11 microdelletions in DiGeorge and velocardiofacial syndromes: Implications for genetic counseling and prenatal diagnosis. J Med Genet 30:813–817, 1993
Sakai T, Matsuoka M, Aoki M, Nosaka K, Mitsuya H: Missense mutation of the interleukin-12 receptor β1 chain-encoding gene is associated with impaired immunity against mycobacterium avium complex infection. Blood 97:2688–2694, 2001
Monis-Teisserenc HT, Gadola SD, Cella M: Association of a syndrome rembling Wegener's granulomatosis with low surface expression of HLA-class-I molecules. Lancet 354:1598–1603, 1999
Report on Registration of Births and Deaths, 2004. Registry of Births and Deaths, National Registration Department, Taiwan
Chapel HM, Webster ADB: Assessment of the immune system. In Primary Immunodeficiency Diseases, HD Ochs, CIE Smith, JM Puck (eds). New York, Oxford, 1999, pp 419–431
Quartier P, Debre M, De Blic J, de Sauverzac R, Sayegh N, Jabado N, Haddad E, Blanche S, Casanova JL, Smith CI, Le Deist F, de Saint Basile G, Fischer A: Early and prolonged intravenous immunoglobulin replacement therapy in childhood aggammaglobulinemia: a retrospetic survey of 31 patients. J Pediatr 134:589–596, 1999
Lim DL, Thong BY, Ho SY, Shek LP, Lou J, Leong KP, Chng HH, Lee BW: Primary immunodeficiency diseases in Singapore-the last 11 years. Singapore Med J 44:579–586, 2003
Fasth A: Primary immunodeficiency disorders in Sweden: cases among children. 1974–1979. J Clin Immunol 2:86–92, 1982
Buckley RH, Fischer A: Bone marrow transplantation for primary immunodeficiency diseases. In Primary Immunodeficiency Diseases, HD Ochs, CIE Smith, JM Puck (eds). New York, Oxford, 1999, pp 459–475
Buckley RH, Schiff SE, Schiff RI, Markert L, Williams LW, Roberts JL, Myers LA, Ward FE: Hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency. N Engl J Med 340:508–516, 1999
Knutsen AP, Wall DA: Kinetics of T-cell development of umbilical cord blood transplantation in severe T-cell immunodeficiency disorders. J Allergy Clin Immunol 103:823–832, 1999
Bhattacharya A, Slatter M, Curtis A, Chapman CE, Barge D, Jackson A, Flood TJ, Abinun M, Cant AJ, Gennery AR: Successful umbilicord blood stem cell transplantation for chronic granulomatous disease. Bone Marrow Transplant 31:403–405, 2003
Ozsahin H, Le Deist F, Benkerrou M, Cavazzana-Calvo M, Gomez L, Griscelli C, Blanche S, Fischer A: Bone marrow transplantation in 26 patients with Wiskott-Aldrich syndrome from a single center. J Pediatr 129:238–244, 1996
Ziegner UH, Ochs HD, Schanen C, Feig SA, Seyama K, Futatani T, Gross T, Wakim M, Roberts RL, Rawlings DJ, Dovat S, Fraser JK, Stiehm ER: Unrelated umbilical cord stem cell transplantation for X-linked immunodeficiencies. J Pediatr 138:570–573, 2001
Ohtsuka Y, Shimizu T, Nishizawa K, Ohtaki R, Someya T, Noguchi A, Shimura N, Kim H, Sugimoto H, Fujita H, Morio T, Yamashiro Y: Successful engraftment and decrease of cytomagalovirus load after cord blood stem cell transplantation in a patient with DiGeorge syndrome. Eur J Pediatr 163:747–748, 2004
Thomson BG, Robertson KA, Gowan D, Heilman D, Broxmeyer HE, Emanuel D, Kotylo P, Brahmi Z, Smith FO: Analysis of engraftment, graft-versus-host disease, and immune recovery following unrelated donor cord blood transplantation. Blood 96:2703–2711, 2000
Grimbacher B, Hutloff A, Schlesier M, Glocker E, Warnatz K, Drager R, Eibel H, Fischer B, Schaffer AA, Mages HW, Kroczek RA, Peter HH: Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency. Nat Immunol 4:261–268, 2003
Yan M, Wang H, Chan B, Roose-Girma M, Erickson S, Baker T, Tumas D, Grewal IS, Dixit VM: Activation and accumulation of B cells in TACI-deficient mice. Nat Immunol 2:638–643, 2001
Thompson JS, Bixler SA, Qian F, Vora K, Scott ML, Cachero TG, Hession C, Schneider P, Sizing ID, Mullen C, Strauch K, Zafari M, Benjamin CD, Tschopp J, Browning JL, Ambrose C: BAFF-R, a newly identified TNF receptor that specifically interacts with BAFF. Science 293:2108–2111, 2001
Castigli E, Wilson SA, Scott S, Dedeoglu F, Xu S, Lam KP, Bram RJ, Jabara H, Geha RS: TACI and BAFF-R mediate isotype switching in B cells. J Exp Med 201:35–39, 2005
Warnatz K, Salzer U, Gutenberger S, Schlesier M, Grimbacher B, Peter HH, Eibel H: Finally found: Human BAFF-R deficiency causes hypogammaglobulinemia. Clin Immunol Suppl:S20, 2005 [abstract]
Salzer U, Chapel HM, Webster AD, Pan-Hammarstrom Q, Schmitt-Graeff A, Schlesier M, Peter HH, Rockstroh JK, Schneider P, Schaffer AA, Hammarstrom L, Grimbacher B: Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans. Nat Genet 37:820–828, 2005
Castigli E, Wilson SA, Garibyan L, Rachid R, Bonilla F, Schneider L, Geha RS: TACI is mutant in common variable immunodeficiency and IgA deficiency. Nat Genet 37:829–834, 2005
Castano D, Patino PJ, Woellner C, Salzer U, Grimbacher B, Montoya CJ, Orrego JC, Rugeles C, Franco JL: Novel humoral immunodeficiency in humanns associated with deleterious homozygous mutation in CD19. Clin Immunol Supp1:S29, 2005 [abstract]
Chiocchetti A, Mesturini R, Bensi T, Biava A, Ferretti M, Santoro C, Pignata C, Rieux-Laucat F, Dianzani I, Ramenghi U, Notarangelo LD, Dianzani U: Hypogammaglobulinemia and lymphoproliferation in two patients with heterozygous deleterious mutation of the Caspase-9 gene. Clin Immunol Supp1:S241, 2005 [abstract]
ACKNOWLEDGMENTS
The authors would like to thank Bor-Luen Chiang MD, PhD in National Taiwan University hospital (NT), Shyh-Dar Shyur MD in Mackay memorial hospital (MK), Wen-Jue Soong MD in Veterans hospital (Ve), and Shyh-Shin Chiou MD, PhD in Kaohsing University hospital (Ks) for the referrals, all participating patients and families for their kind cooperation. We also wish to express our gratitude to Mai-Tzu Chen, Hsiu-Li Chou and Hsiu-Shan Hsiao for their technical assistance. This study was supported in part by Chang-Gung Medical Research Progress grants (CMRPG 32069 awarded to W.I. Lee and 32003 to J.L. Huang) and National Science Council grants (NMRPG 3131 and C 93-2314-B-182A-111 to W.I. Lee and 3116 to J.L. Huang).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lee, WI., Jaing, TH., Hsieh, MY. et al. Distribution, Infections, Treatments and Molecular Analysis in a Large Cohort of Patients with Primary Immunodeficiency Diseases (PIDs) in Taiwan. J Clin Immunol 26, 274–283 (2006). https://doi.org/10.1007/s10875-006-9013-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10875-006-9013-7