immunosuppresive antibodies

Immunosuppresive Antibodies

Dr Nikhil BansalDr Nikhil Bansal

J.N.M.C.,WardhaJ.N.M.C.,Wardha

Types

Antilymphocyte & Antithymocyte antibodies

Muromonab - CD3 Immune Globulin Intravenous (IGIV) Anti-D Immunoglobulin Hyperimmune Immunoglobulins

Antilymphocyte (ALG) & Antithymocyte (ATG)

Antibodies

Polyclonal antibodies

Obtained by immunization of large animals (horses or sheep) with human lymphoid cells.

ATG binds to T-lymphocytes & depletes them.

ALG acts primarily on small long lived peripheral lymphocytes.

Destruction or inactivation of T-cells

Impairment of delayed HSR & cellular

immunity

*While humoral Ab formation remains relatively intact.

Uses

As a potent immunosuppressant To suppress acute allograft rejection

episodes. Management of solid organ or bone

marrow transplantation. In induction regimens.

Adverse effects

Local pain & erythema at the site

of inj(type3 HS)

Anaphylactic reaction

Serum sickness reactions to ALG

Muromonab-CD3

A murine monoclonal antibody against CD3 glycoprotein

Binding of Muromonab-CD3 to CD-3 Ag

Obstruction of binding of MHC 2 Ag complex to the T-cell receptor

Ag recognition is interfered

Precipitation of T-cell in immune response is prevented

T-cell rapidly disappear from circulation

IMMUNE BLOCK STAGE

Uses

As induction therapy together with corticosteroids & azathioprine with delayed use of cyclosporine in ‘sequential regimen’ for organ transplant

Also valuable for steroid resistance rejection reactions & has been use to deplete T-cells from donor bone marrow before transplant

Adverse effect

It initially may produce ‘cytokine release’ syndrome with flu like symptoms: chills, rigor, wheezing, occasionally aseptic meningitis.

* High dose of corticosteroid pretreatment reduce the reaction.

Immune Globulin Intravenous (IGIV) A quit different approach to

immunomodulation is the i.v. use of polyclonal human immunoglobulin.

This Ig (usually IgG) is prepared from pools of thousands of healthy donors & no specific Ab is targeted.

Its precise mech. of action is still controversial.

Possible Mechanism Of Action of IGIV

It includes reduction of Helper T-cells Increase of suppressor T-cells Decrease of spontaneous Ig

production Fc receptor blockade Increase Ab catabolism & Idiotypic-anti-idiotypic interactions

with “pathologic antibodies”

Uses

It is effective in: Ig deficiency Autoimmune disorder HIV Bone marrow transplants SLE & Idiopathic, thrombocytopenic

purpura.

Anti-D Immunoglobulin

Human IgG having high titre of Ab against Rh (D) antigen.

Binds to Rh Ag & does not allow them to induce antibody formation in Rh –ve individuals.

Used for prevention of post partum formation Ab in Rh-D negative.

Hyper immune Immunoglobulin

IGIV preparations made from pools of selected human or animal donors with high titre of antibody against particular agents of interest (viruses and toxins)

Intravenous administration of hyper immune globulins is passive transfer of high titre antibody that either reduces risk or severity of infection.

Uses

Various hyper immune IGIV are available for treatment of Respiratory Syncytial Virus, Cytomegalo Virus, Vericella Zoster, Hepatitis B, tetanus, rabies and digoxin overdose.

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