Immunological Markers in Children with Genetic Disorders and Recurrent Respiratory Tract Infections

Authors

  • Shams Kholoussi Department of Immunogenetics, National Research Centre, Dokki, Cairo, Egypt
  • Naglaa Kholoussi Department of Immunogenetics, National Research Centre, Dokki, Cairo, Egypt
  • Hala El Nady Department of Child Health, National Research Centre, Dokki, Cairo, Egypt
  • Engy A. Ashaat Department of Clinical Genetics, National Research Centre, Dokki, Cairo, Egypt
  • Rania Fawzy Mahmoud Abdelkawy Department of Immunogenetics, National Research Centre, Dokki, Cairo, Egypt
  • Asem Metwally Abo-Shanab Department of Immunogenetics, National Research Centre, Dokki, Cairo, Egypt

DOI:

https://doi.org/10.3889/oamjms.2020.3861

Keywords:

Mannose-binding lectin 2, Immunoglobulins, Flow cytometry, Genetic disorders, Recurrent respiratory tract infections

Abstract

BACKGROUND: Recurrent respiratory tract infections (RRI) are one of the extremely high common reasons for pediatric visits and hospitalization. Immunodeficiencies are considered as important conditions that may increase the probability of occurrence of RRI. Mannose-binding lectin (MBL2) is a protein of the innate immune system involved in the opsonization and the complement activation. MBL2 deficiency is associated with infectious diseases mainly chest infections; however, subnormal MBL2 levels are also seen in healthy subjects. Primary immunedeficiencies are associated with recurrent infections which mainly appear in early childhood.

AIM: The aim of the study was to estimate T and B and natural killer cells percentage and to investigate the MBL2 and immunoglobulins (Igs) serum levels in children with recurrent RRIs in different genetic disorders compared to normal control.

METHODS: This study included 50 children having a history of recurrent RRIs. All patients had genetic disorders and referred to National Research Centre for follow-up, in addition to, 25 children, age- and sex-matched as a healthy control group. They were subjected to full clinical examination and laboratory investigations including complete blood count (CBC), CD3, CD4, CD8, CD16, and CD19 by flow cytometry, MBL2 by enzyme-linked immunosorbent assay (ELISA), and Igs serum concentrations by nephelometry.

RESULTS: CD16 showed a non-statistical significant difference between both patient groups. Serum levels of IgA in patient groups showed a significant decrease compared to the control group. Moreover, the serum level of IgM results shows a highly significant decrease when compared with the control group. There was no statistically significant difference in MBL2 and IgG serum levels between patient groups and control group.

CONCLUSION: Children with genetic disorders and recurrent RRIs showed a statistically significant decrease of IgA and IgM serum levels as compared to the control group, while the serum level of MBL2 did not show significant results.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Soler-Palacín P, de Gracia J, González-Granado LI, Martín C, Rodríguez-Gallego C, Sánchez-Ramón S, et al. Primary immunodeficiency diseases in lung disease: Warning signs, diagnosis and management. Respir Res. 2018;19(1):219. https://doi.org/10.1186/s12931-018-0923-8 PMid:30419907

Cohen R, Just J, Koskas M, Bingen E, Boucherat M, Bourrillon A, et al. Recurrent respiratory tract infections: How should we investigate and treat? Arch Pediatr. 2005;12(2):183-90. PMid:15694546

Garred P, Larsen F, Seyfarth J, Fujita R, Madsen HO. Mannose-binding lectin and its genetic variants. Genes Immun. 2006;7(2):85-94. https://doi.org/10.1038/sj.gene.6364283 PMid:16395391

Turner MW, Dinan L, Heatley S, Jack DL, Boettcher B, Lester S, et al. Restricted polymorphism of the mannose-binding lectin gene of indigenous Australians. Hum Mol Genet. 2000;9(10):1481-6. https://doi.org/10.1093/hmg/9.10.1481 PMid:10888598

Summerfield JA. Clinical potential of mannose-binding lectin-replacement therapy. Biochem Soc Trans. 2003;31(Pt 4):770-3. https://doi.org/10.1042/bst0310770 PMid:12887301

Sullivan K, Winkelstein J. Deficiency of the complement system. In: Stiehm ER, Ochs HD, Winkelstein JA. editors. Immunologic Disorders in Infants and Children. 5th ed. Philadelphia, PA: Elsevier Saunders; 2004. p. 652-84. http:// dx.doi.org/10.1136/adc.2004.061770

Cedzynski M, Swierzko AS, Kilpatrick DC. Factors of the lectin pathway of complement activation and their clinical associations in neonates. J Biomed Biotechnol. 2012;2012:363246. https:// doi.org/10.1155/2012/363246 PMID: 22619494

Picard C, Al-Herz W, Bousfiha A, Casanova JL, Chatila T, Conley ME, et al. Primary immunodeficiency diseases: An update on the classification from the international union of immunological societies expert committee for primary immunodeficiency 2015. J Clin Immunol. 2015;35(8):696-726. https://doi.org/10.3389/fimmu.2014.00460 PMid:26482257

Bazregari S, Azizi G, Tavakol M, Asgardoon MH, Kiaee F, Tavakolinia N, et al. Evaluation of infectious and non-infectious complications in patients with primary immunodeficiency. Cent Eur J Immunol. 2017;42(4):336-41. https://doi.org/10.5114/ ceji.2017.72825 PMid:29479289

Kanegane H, Hoshino A, Okano T, Yasumi T, Wada T, Takada H, et al. Flow cytometry-based diagnosis of primary immunodeficiency diseases. Allergol Int 2018;67(1):43-54. https://doi.org/10.1016/j.alit.2017.06.003 PMid:28684198

Schroeder HW Jr., Cavacini L. Structure and function of immunoglobulins. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S41-52. https://doi.org/10.1016/j. jaci.2009.09.046 PMid:20176268

Notarangelo LD. Primary immunodeficiencies. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S182-94. https://doi. org/10.1016/j.jaci.2009.07.053 PMid:20042228

Olinder-Nielsen AM, Granert C, Forsberg P, Friman V, Vietorisz A, Björkander J. Immunoglobulin prophylaxis in 350 adults with IgG subclass deficiency and recurrent respiratory tract infections: A long-term follow-up. Scand J Infect Dis. 2007;39(1):44-50. https://doi.org/10.1080/00365540600951192 PMid:17366012

Bermejo-Martin JF, Giamarellos-Bourboulis EJ. Endogenous immunoglobulins and sepsis: New perspectives for guiding replacement therapies. Int J Antimicrob Agents. 2015;46(Suppl 1):S25-8. https://doi.org/10.1016/j. ijantimicag.2015.10.013 PMid:26597932

Shearer WT, Rosenblatt HM, Gelman RS, Oyomopito R, Plaeger S, Stiehm ER, et al. Lymphocyte subsets in healthy children from birth through 18 years of age: the Pediatric AIDS Clinical Trials Group P1009 study. J Allergy Clin Immunol. 2003;112(5):973-80 https://doi.org/10.1016/j.jaci.2003.07.003 PMid:14610491

Trevisiol C, Boniotto M, Giglio L, Poli F, Morgutti M, Crovella S. MBL2 polymorphisms screening in a regional Italian CF center. J Cyst Fibros. 2005;4(3):189-91. https://doi.org/10.1016/j. jcf.2005.04.001 PMid:16046196

Stepensky P, Keller B, Shamriz O, von Spee-Mayer C, Friedmann D, Shadur B, et al. T+ NK+ IL-2 receptor γ chain mutation: A challenging diagnosis of atypical severe combined immunodeficiency. J Clin Immunol. 2018;38(4):527-36. https:// doi.org/10.1007/s10875-018-0514-y PMid:29948574

Atan O, Kucukcelebi A, Atik T, Ozkınay F. Mannose binding lectin codon 54 polymorphism and susceptibility to recurrent respiratory tract infections in children: A meta-analysis. Int J Pediatr Otorhinolaryngol. 2016;81:41-5. https://doi. org/10.1016/j.ijporl.2015.11.029 PMid:26810288

Jørgensen CM, Jensen L, Christiansen M, Bjerre M, Jensen JMB, Thiel S. Pattern recognition molecules of the lectin pathway-screening of patients with suspected immunodeficiency. J Clin Immunol. 2019;39(7):668-77. https:// doi.org/10.1007/s10875-019-00675-8 PMid:31377972

Siljan WW, Holter JC, Nymo SH, Husebye E, Ueland T, Skattum L, et al. Low levels of immunoglobulins and mannose-binding lectin are not associated with etiology, severity, or outcome in community-acquired pneumonia. Open Forum Infect Dis. 2018;5(2):ofy002. https://doi.org/10.1093/ofid/ofy002 PMid:29410975

Ishii M, Ohsawa I, Inoshita H, Kusaba G, Onda K, Wakabayashi M, et al. Serum concentration of complement components of the lectin pathway in maintenance hemodialysis patients, and relatively higher levels of L-Ficolin and MASP-2 in Mannose-binding lectin deficiency. Ther Apher Dial. 2011;15(5):441-7. https://doi.org/10.1111/j.1744-9987.2011.00936.x PMid:21974696

Roy S, Knox K, Segal S, Griffiths D, Moore CE, Welsh KI, et al. MBL genotype and risk of invasive pneumococcal disease: A case-control study. Lancet. 2002;359(9317):1569-73. https:// doi.org/10.1016/s0140-6736(02)08516-1 PMid:12047967

Koch A, Melbye M, Sorensen P, Homoe P, Madsen HO, Molbak K, et al. Acute respiratory tract infections and mannose-bindinglectininsuff/iciency during early childhood. JAMA. 2001;285(10):1316. https://doi.org/10.1001/jama.285.10.1316

Dahl M, Tybjaerg-Hansen A, Schnohr P, Nordestgaard BG. A population-based study of morbidity and mortality in mannose-binding lectin deficiency. J Exp Med. 2004;199(10):1391-9. https://doi.org/10.1084/jem.20040111 PMid:15148337

Hoeflich C, Unterwalder N, Schuett S, Schmolke K, Boenisch O, Hammer M, et al. Clinical manifestation of mannose-binding lectin deficiency in adults independent of concomitant immunodeficiency. Hum Immunol. 2009;70(10):809-12. https:// doi.org/10.1016/j.humimm.2009.07.003 PMid:19580835

Rantala A, Lajunen T, Juvonen R, Bloigu A, Silvennoinen- Kassinen S, Peitso A, et al. Mannose-binding lectin concentrations, MBL2 polymorphisms, and susceptibility to respiratory tract infections in young men. J Infect Dis. 2008;198(8):1247-53. https://doi.org/10.1086/591912 PMid:18729778

Siebert JN, L’huillier AG, Grillet S, Delhumeau C, Siegrist CA, Posfay-Barbe KM. Memory B cell compartment constitution and susceptibility to recurrent lower respiratory tract infections in young children. J Leukoc Biol. 2013;93(6):951-62. https://doi. org/10.1189/jlb.0312117 PMid:23530161

Mahlaoui N. Immune explorations on children suffering from recurrent respiratory tract infections. Arch Pediatr. 2007;14:S203- 7. https://doi.org/10.1016S0929-693X(07)78707-9 PMID: 18280912

Kholoussi S, Kholoussi N, Zaki ME, El-Bassyouni HT, Elnady H, Morcos B, et al. Immunological evaluation in patients with familial mediterranean fever. Open Access Maced J Med Sci. 2018;6(2):310-3. https://doi.org/10.3889/oamjms.2018.079 PMid:29531594

Raniszewska A, Górska E, Kotuła I, Stelmaszczyk-Emmel A, Popko K, Ciepiela O. Recurrent respiratory tract infections in children analysis of immunological examinations. Cent Eur J Immunol. 2015;40(2):167-73. https://doi.org/10.5114/ ceji.2015.52830 PMid:26557030

Jenesak M, Ciljakova M, Rennerova Z, Babusikova E, Banovcin P. Recurrent Respiratory Infections in Children Definition, Diagnostic Approach, Treatment and Prevention Bronchitis. Karnataka: InTech; 2011. https://doi.org/10.5772/19422

Lear S, Condliffe A. Respiratory infection and primary immune deficiency - what does the general physician need to know? J R Coll Physicians Edinb. 2014;44(2):149-55. https://doi. org/10.4997/jrcpe.2014.214 PMid:24999779108

Downloads

Published

2020-02-05

How to Cite

1.
Kholoussi S, Kholoussi N, El Nady H, Ashaat EA, Abdelkawy RFM, Abo-Shanab AM. Immunological Markers in Children with Genetic Disorders and Recurrent Respiratory Tract Infections. Open Access Maced J Med Sci [Internet]. 2020 Feb. 5 [cited 2024 Nov. 21];8(B):104-8. Available from: https://oamjms.eu/index.php/mjms/article/view/3861