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Summer Research Fellowship Programme of India's Science Academies

Immunobiology of Hemoglobin

Mansi Mulay

Guru Nanak Khalsa College, Nathalal Parekh Marg, Matunga, Mumbai, Maharashtra 400019

Dr Rahul Pal

National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, Delhi 110067

Abstract

Autoimmune responses are generated when the immune system fails to distinguish between self and non-self moieties, a phenomenon that may result in an autoimmune disease. Such diseases can be classified as either organ-specific or systemic. Diabetes mellitus Type 1 is an example of the former, and Systemic Lupus Erythematosus (SLE or lupus) is an example of the latter. In SLE, auto-antibodies to more than a hundred and eighty moieties are observed, with cytoplasmic, cell surface and nuclear antigens all being targeted. Pathological effects of disease on the kidneys, skin, brain, lungs, heart, liver and the hematopoietic system have been documented. SLE is a complex interplay of genetic, environmental and hormonal factors.

Hemoglobin (Hb), an inflammatory molecule, is being studied as an antigenic and immunogenic agent in lupus in the lab. Under physiological conditions, hemoglobin binds to haptoglobin (Hp), and the complex is cleared via CD163-mediated endocytosis. In lupus, Hb concentrations can overwhelm available Hp levels (and other clearance mechanisms), leading to the presence of free Hb. Hb, as well as free heme, have well-documented inflammatory and toxic effects.

The lab has previously described the preferential Hb-mediated release of lupus-associated cytokines from splenocytes derived from aging, lupus-prone mice. Anti-Hb autoantibodies have been observed in such mice and in SLE patients.

Keywords: Autoimmunity, Systemic Lupus Erythematosus, Hemoglobin.

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