Higher minor hemoglobin A2 levels in multiple sclerosis patients correlate with lesser disease severity

Özcan, Muhammed Emin; Ince, Bahri; Karadeli, Hasan Hüseyin; Gedikbaşı, Asuman; Asıl, Talip; Altinöz, Meriç A.

doi:10.2147/ndt.s109954

Cited by 7 publications

(1 citation statement)

References 32 publications

(49 reference statements)

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“…It has been reported that multiple sclerosis patients treated with IFNb have higher levels of HbA2 in comparison to those treated with other drugs (26). For the purpose of verifying whether therapy with IFNb was the cause of the increase in HbA2 in vivo, we performed a study in MS patients.…”

Section: Hemoglobin A2 Levels Increase After Ifnb Treatments In Multimentioning

confidence: 99%

Delta-Globin Gene Expression Is Enhanced in vivo by Interferon Type I

et al. 2020

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Beta hemoglobinopathies are widely spread monogenic lethal diseases. Delta-globin gene activation has been proposed as a possible approach for curing these pathologies. The therapeutic potential of delta-globin, the non-alpha component of Hemoglobin A 2 (α2δ2; HbA2), has been demonstrated in a mouse model of beta thalassemia, while its anti-sickling effect, comparable to that of gamma globin, was established some time ago. Here we show that the delta-globin mRNA level is considerably increased in a Deoxyribonuclease II-alpha knockout mouse model in which type 1 interferon (interferon beta, IFNb) is activated. IFNb activation in the fetal liver improves the delta-globin mRNA level, while the beta-globin mRNA level is significantly reduced. In addition, we show that HbA2 is significantly increased in patients with multiple sclerosis under type 1 interferon treatment. Our results represent a proof of principle that delta-globin expression can be enhanced through the use of molecules. This observation is potentially interesting in view of a pharmacological approach able to increase the HbA2 level.

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Section: Hemoglobin A2 Levels Increase After Ifnb Treatments In Multimentioning

confidence: 99%

Delta-Globin Gene Expression Is Enhanced in vivo by Interferon Type I

et al. 2020

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Correlation of geographic distributions of haptoglobin alleles with prevalence of multiple sclerosis (MS) – a narrative literature review

2016

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We have proposed that the myelin damage observed in multiple sclerosis (MS) may be partly mediated through the long-term release and degradation of extracellular hemoglobin (Hb) and the products of its oxidative degradation [Cellular and Molecular Life Sciences, 71, 1789-1798, 2014]. The protein haptoglobin (Hpt) binds extracellular Hb as a first line of defense, and can serve as a vascular antioxidant. Humans have two different Hpt alleles: Hpt1 and Hpt2, giving either homozygous Hpt1-1 or Hpt2-2 phenotypes, or a heterozygous Hpt1-2 phenotype. We questioned whether those geographic regions with higher frequency of the Hpt2 allele (conversely, lower frequency of Hpt1 allele) would correlate with an increased incidence of MS, because different Hpt phenotypes will have variable anti-oxidative potentials in protecting myelin from damage inflicted by extracellular Hb and its degradation products. To test this hypothesis, we undertook a systematic analysis of the literature on reported geographic distributions of Hpt alleles to compare them with data reported in the World Health Organization Atlas of worldwide MS prevalence. We found the frequency of the Hpt1 allele to be low in European and North American countries with a high prevalence of MS, consistent with our hypothesis. However, this correlation was not observed in China and India, countries with the lowest Hpt1 frequencies, yet low reported prevalence of MS. Nevertheless, this work shows the need for continued refinement of geographic patterns of MS prevalence, including data on ethnic or racial origin, and for new clinical studies to probe the observed correlation and evaluate Hpt phenotype as a predictor of disease variability and progression, severity, and/or comorbidity with cardiovascular disorders.

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