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Filarial Abundant Larval Transcript Protein ALT-2: An Immunomodulatory Therapeutic Agent for Type 1 Diabetes

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Abstract

Type 1 diabetes (T1D) that accounts for about 5–10 % of all diabetes cases results from the autoimmune destruction of the insulin-producing beta cells in the pancreas. It is characterized by severe inflammatory reaction mediated by pronounced T helper type-1 response. Parasitic infections having the ability to skew the host immune responses towards type-2 type as a part of their defense mechanism are able to induce protection against autoimmune diseases like T1D. Hence, the present study is undertaken to explore a recombinant abundant larval transcript protein of the human lymphatic filarial parasite Brugia malayi (rBmALT-2), a known anti-inflammatory molecule for its therapeutic effect on streptozotocin (STZ)-induced T1D in mice. The diabetic mice on treatment with rBmALT-2 showed a significant (p < 0.0005) decrease in their fasting blood glucose levels. By the end of the second week after the initiation of treatment with the rBmALT-2, 28 % of the diabetic mice became normal and none of them were diabetic by the end of 5th week. The anti-diabetic effect of rBmALT-2 significantly correlated with the concomitant redressal of the pancreatic histopathological damage caused by STZ assault (rho = 0.87; p < 0.0005). The sera of rBmALT-2 treated diabetic mice had increased levels of IgG1 antibodies associated with decreased IgG2a antibodies against the principal autoantigen insulin. The splenocyte proliferative response and the cytokine release in the treated mice showed marked bias against inflammation skewing the immune response to Th-2 type. From this study, it can be envisaged that that filarial proteins like rBmALT-2 with effective immunomodulatory activity and anti-diabetic effect are promising alternative therapeutic agents for T1D.

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Acknowledgments

This research work was supported by the funding received from Department of Biotechnology (DBT) (Project Id. BT/PR/4988/INF/22/155/2012) and Department of Science and Technology (DST-FIST) (Project Id. SR/FST/LSI-470/2010) of Ministry of Science and Technology, Government of India. The authors are also thankful to Indian Council of Medical Research, Government of India for the STS Fellowship support to the first author.

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Authors and Affiliations

  1. Department of Biochemistry and JB Tropical Disease Research Centre, Mahatma Gandhi Institute of Medical Sciences, Sevagram, MS, 442102, India

    Sridhar M. Reddy, Nitin Amdare, Vishal Khatri, Kalyan Goswami & Maryada Venkata Rami Reddy

  2. Department of Pharmacology, Sri Aurobindo Institute of Medical Sciences, Indore, MP, 453555, India

    Pooja M. Reddy

  3. Department of Anatomy, Mahatma Gandhi Institute of Medical Sciences, Sevagram, MS, 442102, India

    Aaditya Tarnekar

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  1. Sridhar M. Reddy
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  2. Pooja M. Reddy
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  3. Nitin Amdare
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  4. Vishal Khatri
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  5. Aaditya Tarnekar
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  6. Kalyan Goswami
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  7. Maryada Venkata Rami Reddy
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Correspondence to Maryada Venkata Rami Reddy.

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All the authors have declared that they have no conflict of interest.

Ethical Approval

This study does not contain any studies with human participants performed by any of the authors. This study was approved by Institutional Animal Ethics Committee and national guidelines as per Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA) for the care and use of animals were followed.

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Reddy, S.M., Reddy, P.M., Amdare, N. et al. Filarial Abundant Larval Transcript Protein ALT-2: An Immunomodulatory Therapeutic Agent for Type 1 Diabetes. Ind J Clin Biochem 32, 45–52 (2017). https://doi.org/10.1007/s12291-016-0572-y

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  • DOI: https://doi.org/10.1007/s12291-016-0572-y

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