Peculiarities of humoral immunity parameters in newborns with markers of undifferentiated connective tissue dysplasia

Authors

DOI:

https://doi.org/10.15574/SP.2024.6(142).614

Keywords:

newborns, immunity, serum immunoglobulins, connective tissue dysplasia

Abstract

Connective tissue dysplasia can affect the immune response in children. The study of humoral immunity indicators in newborns with locomotor and biochemical markers of undifferentiated connective tissue dysplasia (UCTD) is very relevant.

Aim - study the correlations between anthropometric, laboratory markers of UCTD and indicators of the B-cell link of immunity in newborns.

Materials and methods. We examined 122 newborns: 79 full-term and 43 premature infants. In them, the perinatal history data were analyzed, anthropometric and biochemical (matrix metalloproteinase-1 (MMP-1), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1)) markers of UCTD were studied, and the ratio of MMP-1/TIMP-1 was calculated. The absolute number of B-lymphocytes and the levels of immunoglobulins of classes A (IgA), M (IgM), G (IgG) in the blood were also investigated. The main group (n=82) consisted of newborns with elevated values of ≥2 anthropometric markers of UCTD, the control group (n=40) included children without deviation from the norm of any anthropometric index.

Results. Children with signs of UCTD are more likely to be born from ≥2 births, with a body weight of 2499-2000 g and ≤1999 g, and have lower levels of serum IgA, IgM than children of the control group. Such perinatal factors as operative delivery and parity of more than two births can be considered prognostically unfavorable for a lower absolute number of B-lymphocytes, lower levels of IgA and IgM in the blood of newborns. Serum content of MMP-1≥4.51 ng/ml, values of MMP-1/TIMP-1≥0.31 are associated with a higher absolute number of B-lymphocytes and lower level of IgA, also the concentration of TIMP-1≥16.08 ng/ml is associated with higher levels of IgA, IgM, IgG. The content of serum immunoglobulins correlates with the gestational age.

Conclusions. Therefore, newborns with anthropometric markers of UCTD and an imbalance of biochemical markers (MMP-1, TIMP-1, index MMP-1/TIMP-1) have lower levels of serum IgA and IgM. The concentration of MMP-1≥4.51 ng/ml, MMP-1/TIMP-1≥0.31, TIMP-1≤16.07 ng/ml are prognostically unfavorable factors regarding changes in the B-cell immunity in newborns. The lowest concentrations of immunoglobulins of all classes were recorded in children with a gestational age of 31-28 weeks.

The study was carried out according to the principles of the Declaration of Helsinki. The study protocol was accepted by the Local Ethical Committee of these institutions. The informed consent of the children's parents was obtained for the research.

The authors declare no conflict of interest.

Author Biography

O.Yu. Chumak, Shupyk National Healthcare University of Ukraine, Kyiv

Lugansk State Medical University, Rivne, Ukraine

References

Abbakumova LN, Arsentev VG, Gnusaev SF, Kadurina TI, Trisvetova EL et al. (2016). Multifactorial and hereditary connective tissue disorders in children. Diagnostic algorithms. Management tactics. Pediatrician. 7 (2): 5-39. https://doi.org/10.17816/PED725-39

Arese V, Murabito P, Ribero S et al. (2019). Autoimmune connective tissue diseases and pregnancy. Italian Journal of Dermatology and Venereology. 154 (3): 263-276. https://doi.org/10.23736/S0392-0488.18.06252-1; PMid:30650958

Barchan HS. (2021). Chastota i kharakter imunnykh porushen pry rekurentnykh respiratornykh infektsiiakh ta u razi yikh perebihu na tli nedyferentsiiovanoi dysplazii spoluchnoi tkanyny. Zbirnyk tez naukovykh robit uchasnykiv mizhnarodnoi naukovo-praktychnoi konferentsii «Medychna nauka ta praktyka XXI stolittia». Kyiv, 5-6 liutoho 2021 r. Ukrainskyi zhurnal ekstremalnoi medytsyny im. H.O. Mozhaieva. 4: 5-13.

Barchan HS. (2020). Optymizatsiia prohnozuvannia perebihu ta profilaktyky rekurentnykh respiratornykh infektsii u ditei. Dys. na zdobuttia nauk. stupenia kandydata medychnykh nauk: spets.: 14.01.10 - pediatriia: 186. URL: http://repo.knmu.edu.ua/handle/123456789/31577.

Cabral-Pacheco GA, Garza-Veloz I, Castruita-De la Rosaet C et al. (2020). The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases. Int. J. Mol. Sci. 21(24): 55. https://doi.org/10.3390/ijms21249739; PMid:33419373 PMCid:PMC7767220

Caner I, Koca E, Özdemir Ö. (2021). Serum Levels of Immunoglobulin Isotypes and Immunoglobulin G Subtypes in Healthy Term Turkish Newborns. Nig J Clin Pract. 24(7): 1061-1066. https://doi.org/10.4103/njcp.njcp_294_20; PMid:34290183

Chernyshova LI, Lapii FI, Volokha AP ta in. (2018). Imunoprofilaktyka infektsiinykh khvorob. Navch.-metod. posib. Za red. L.I. Chernyshovoi, F.I. Lapiia, A.P. Volokhy. K.: VSV «Medytsyna»: 304.

Chernyshova LI, Volokha AP, Kostiuchenko LV ta in. (2013). Dytiacha imunolohiia. Pidruchnyk. Za red. prof. L.I. Chernyshovoi, A.P. Volokhy. K.: VSV «Medytsyna»: 720.

Chumak OYu, Volokha AP. (2021). Pathological conditions in newborns against the background of undifferentiated connective tissue dysplasia in their mothers. Modern Pediatrics. Ukraine. 6(118): 25-31. https://doi.org/10.15574/SP.2021.118.25

Chumak OYu, Volokha AP. (2023). Vyvchennia vzaiemozviazku rivnia matryksnoi metaloproteinazy-1 ta tkanynnoho inhibitoru matryksnoi metaloproteinazy-1 z pokaznykamy imunitetu v novonarodzhenykh ditei. Zbirka materialiv mizhnarodnoi naukovoi konferentsii «Multidisciplinary challenges in contemporary science: innovations and collaboration». September 15, 2023, Lodz, (Poland). Futurity Research Publishing: 338-343.

Chumak OYu, Volokha AP. (2024). The level of serum matrix metalloproteinase-1 and tissue inhibitor of matrix metalloproteinase-1 in newborns from mothers with undifferentiated connective tissue dysplasia. Ukrainian Journal of Perinatology and Pediatrics. 1(97): 64-71. https://doi.org/10.15574/PP.2024.97.64

Cui N, Hu M, Khalil RA. (2017). Biochemical and biological attributes of matrix metalloproteinases. Progress in Molecular Biology and Translational Science. 147: 1-73. https://doi.org/10.1016/bs.pmbts.2017.02.005; PMid:28413025 PMCid:PMC5430303

Ejma-Multański A, Wajda A, Paradowska-Gorycka A. (2023). Cell Cultures as a Versatile Tool in the Research and Treatment of Autoimmune Connective Tissue Diseases. Cells. 12(20): 2489-2511. https://doi.org/10.3390/cells12202489; PMid:37887333 PMCid:PMC10605903

Freitas-Rodríguez S, Folgueras AR, López- Otín C. (2017). The role of matrix metalloproteinases in aging: Tissue remodeling and beyond. Biochim Biophys Acta. 1864(11): 2015-2025. https://doi.org/10.1016/j.bbamcr.2017.05.007; PMid:28499917

Grether JK, Ashwood P, VandeWater J et al. (2016). Prenatal and Newborn Immunoglobulin Levels from Mother-Child Pairs and Risk of Autism Spectrum Disorders. Front. Neurosci. 10(218): 1-10. https://doi.org/10.3389/fnins.2016.00218; PMid:27242422 PMCid:PMC4870252

Lupaltsova O, Drobova N, Servetnyk A. (2022). Congenital immunodeficiency disorders in the pediatric practice. Immunology and Allergy: Science and Practice. 3-4: 21-24. https://doi.org/10.37321/immunology.2022.3-4-03

Mantovani A, Garlanda C. (2023). Humoral Innate Immunity and Acute-Phase Proteins. The new England journal of medicine. 388(5): 439-452. https://doi.org/10.1056/NEJMra2206346; PMid:36724330 PMCid:PMC9912245

Oshlianska OA, Vovk VM. (2018). Osoblyvosti funktsionuvannia mistsevoho imunitetu u ditei z nedyferentsiiovanoiu dysplaziieiu spoluchnoi tkanyny. Ukrainskyi medychnyi chasopys. 2(124); III/IV: 23-26.

Ozdemir SA, Ozer EA, Kose S, Ilhan O, Oztur C, Sutcuoglu S. (2016). Reference values of serum IgG and IgM levels in preterm and term newborns. J Matern Fetal Neonatal Med. Early Online: 1-5. https://doi.org/10.3109/14767058.2015.1027680; PMid:25845271

Palma J, Tokarz-Deptuła B, Deptuła J, Deptuła W. (2018). Natural antibodies - facts known and unknown. Centr Eur J Immunol. 43(4): 466-475. https://doi.org/10.5114/ceji.2018.81354; PMid:30799995 PMCid:PMC6384419

Pollock L, Ridout A, Teh J, Nnadi C, Stavroulias D et al. (2021). The Musculoskeletal Manifestations of Marfan Syndrome: Diagnosis, Impact, and Management. Current Rheumatology Reports. 23: 1-18. https://doi.org/10.1007/s11926-021-01045-3; PMid:34825999 PMCid:PMC8626407

Pou C, Nkulikiyimfura D, Henckel E, Olin A et al. (2019). The repertoire of maternal anti-viral antibodies in human newborns. Nature Medicine. 25: 591-596. https://doi.org/10.1038/s41591-019-0392-8; PMid:30886409

Protsailo MD, Chornomydz YuA, Hnato NM, Vorontsova TO, Chornomydz IB. (2023). Polimorfizm proiaviv dysplatsii spoluchnoi tkanyny u ditei. Aktualni pytannia pediatrii, pediatrii, akusherstva ta hinekolohii. 2: 49-56. https://doi.org/10.11603/24116-4944.2023.2.14337

Protsailo MD, Chornomydz IB, Horishnyi IM, Vorontsova TO. (2022). Syndrom dysplazii spoluchnoi tkanyny v systemi dyspansernoho sposterezhennia simeinoho likaria. Aktualni pytannia pediatrii, pediatrii, akusherstva ta hinekolohii. 1: 95-98. https://doi.org/10.11603/24116-4944.2022.1.13258

Raeeszadeh-Sarmazdeh M, Do LD, Hritz BG. (2020). Metalloproteinases and Their Inhibitors: Potential for the Development of New Therapeutics. Cells. 9(5): 1313. https://doi.org/10.3390/cells9051313; PMid:32466129 PMCid:PMC7290391

Sharma R, Mukhopadhyay K et al. (2022). Immunoglobulin Profile and Lymphocyte Subsets in Preterm Neonates. Ind J Pediatri. 59: 214-217. https://doi.org/10.1007/s13312-022-2470-0; PMid:34992185 PMCid:PMC8964378

Voloshin OM, Chumak OYu. (2017). Undifferentiated connective tissue dysplasia and respiratory diseases in children and adolescents (review of literature). Child's Health. 12(6): 720-727. https://doi.org/10.22141/2224-0551.12.6.2017.112842

Voloshyn OM, Marushko YuV, Hnylytska IP, Masnieva LP. (2020). Rekurentni respiratorni infektsii ta makrobioelementnyi balans u ditei vikom 1-6 rokiv. Visnyk problem biolohii i medytsyny. 1(55): 329-333. https://doi.org/10.29254/2077-4214-2020-1-155-329-333

Xu X, Ng SM, Hassouna E, et al. (2015). Human-derived natural antibodies: biomarkers and potential therapeutics. Future Neurol. 10: 25-39. https://doi.org/10.2217/fnl.14.62; PMid:25678860 PMCid:PMC4321763

Zhuraiev RK. (2012). Syndrom Marfana: evoliutsiia diahnostychnykh kryteriiv. Ukrainskyi medychnyi chasopys. 1(87): 98-102.

Published

2024-10-28

Issue

Section

Original articles