TMPRSS6 gene polymorphism and serum hepcidin in iron deficiency anemia

Background: Iron deficiency anemia [IDA] is a global health problem and common medical condition seen in everyday clinical practice. Hepcidin which is the key regulator of iron homeostasis, that down-regulates iron export by binding to ferroportin which is expressed on the surface of iron-releasing cells, leading to its degradation thus reducing plasma iron levels. Overexpression of hepcidin leads to iron deficiency anemia. Matriptase-2 [MT-2] which is encoded by transmembrane protease serine 6 [TMPRSS6] gene regulates hepcidin expression

Objective: Was to evaluate the role of TMPRSS6 gene polymorphisms and serum hepcidin level in IDA patients

Subjects and methods: This study was carried out on 30 patients with iron deficiency anemia and 30 age and sex matched individuals as control group. Patients were subdivided into [group 1] 14 patients with acquired iron deficiency anemia [IDA] and [group 2]16 patients with iron refractory iron deficiency anemia[IRIDA].TMPRSS6 gene single nucleotide polymorphisms[SNPS], [rs4820268]and[rs855791]were evaluated using real time – polymerase chain reaction [RT-PCR] while serum hepcidin level was measured by enzyme linked immunosorbent assay [ELISA]

Results: There was a significant increase in frequency of the TMPRSS6 SNPs rs855791 and rs 4820268 separately in IRIDA group compared to IDA group,[P=0.003],[P=0.007] respectivelyand to control group[P=0.000] and [P=0.000] respectively. Also, there was highly significant increase in frequency of both mutations together in IRIDA group compared to IDA group [P=0.000] and to control group [P=0.000]. In IDA group there was a significant increase in the frequency of TMPRSS6 SNPs rs 855791 when compared to control group [P=0.013], and a non-significant difference in frequency of SNPs rs 4820268 when compared to control group [P=0.092].Also, there was a non-significant difference in frequency of both mutations together in IDA group in comparison to control group [P> 0.05].There was a highly significant decrease in serum hepcidin level in IDA group and highly significant increase in hepcidin levels in IRIDA group compared to control group [P=0.000].In IRIDA patients group only there was highly significant increase in hepcidin level in those with mutation in both SNPs together [rs4820268 and rs855791] than patients with one mutation or with wild type[P=0.000].There was a significant decrease in Hb and iron and highly significant decrease in MCV, MCH and ferritin in IRIDA patients with mutation of both SNPs together [rs 4820268 and rs855791] compared to one mutation or wild type [P=0.015,0.016,0.002 ,0.000, 0.006 respectively].Also, there was highly significant decrease in Hb, MCV, MCH and ferritin in IDA patients with mutation of both SNPs together[rs 4820268 and rs 855791] compared to one mutation or wild type [P= 0.002,0.002 ,0.004, 0.009 respectively]. In IDA patients there was a significant positive correlation between hepcidin and ferritin [P =0.034, r = 0.279],while there was a significant negative correlation between hepcidin and MCH in IRIDA group [P =0.032, r = - 0.536]

Conclusion: In IRIDA the rs4820268 and rs855791 mutations separately or in combination lack inhibitory effect on hepcidin and consequently iron profile and hemoglobin while in IDA although there was significant increase in frequency of rs855791 mutations, there was no effect on hepcidin which suggests that the rs 4820268 mutation is necessary for affecting hepcidin either alone or in combination with rs 855791 mutation. In IDA, there may be other mechanisms or mutations causing anemia

Assessment of the dynamic immunological interaction between the lactating mothers and their infected nursing infants

Human breast milk is an unique, natural source of nutrition for the human infants which protects them from infections and assists in the development of the infants' intestinal mucosa, gut micro flora and own defenses

The immunomodulatory function of breast milk is thought to be mediated by both cellular and biochemical components, including milk fat globules, immune competent cells, soluble proteins like immunoglobulin [Ig]-A, cytokines and antimicrobial peptides, and bioactive substances like hormones and growth factors. To investigate the effect of active infection in the nursing infants on some immunologic factors [leukocytes, lactoferrin and cathelicidin] in breast milk of their healthy lactating mothers which could be used as a diagnostic tool for assessment of the health status of nursing infants and to ensure the protective role of breast milk. Breast milk from healthy mothers of 15 infants, up to 3 months of age, who were hospitalized with fever, was sampled during active illness and recovery. Another milk samples were taken from mothers of 15 healthy infants of the same ages who served as controls. The total number of leukocytes in all milk samples was counted by Flow Cytometry and the milk levels of lactoferr in and cathelicidin were measured by ELISA. Total CD45[+] leukocytes count, lactoferr in and cathelicidin levels were statistically significantly higher in breast milk of healthy mothers nursing infected infants than that in controls [P-value < 0.001]

These high results of leukocytes, lactoferr in and cathelicidin showed highly statistically significant decrease in the second milk samples were taken from mothers after recovery of infection in their nursing infants when compared to those which were taken during infection [P-value < 0.001]

The correlation between total no. of CD 45 [+] Leukocytes, lactoferr in and cathelicidin levels in SI and in S2, and bet//veen them in SI and the clinical data of the patients showed no statistical significance. Our findings support the dynamic immunological connection between lactating mothers and their nursing infants, especially during active infection that alters the milk to help protect the babies