Immunological mechanisms underlying delayed-type hypersensitivity reactions to glatiramer acetate.

Abstract

BACKGROUND:

Delayed-type hypersensitivity to glatiramer acetate is rare, and the underlying immunological mechanisms are not completely understood.

OBJECTIVE:

To study the immunologic response in 2 patients with multiple sclerosis who developed maculopapular exanthema related with the administration of glatiramer acetate.

METHODS:

The allergologic study included general blood tests, viral serologic tests, and skin tests (patch and intradermal tests). The immunologic study was performed in skin biopsy specimens by immunohistochemistry and in the peripheral blood by flow cytometry and the lymphocyte transformation test.

RESULTS:

Skin test results were negative in both patients, and the diagnosis was confirmed by a drug provocation test. The evaluation of the acute phase showed an increase in the percentage of CD8 T lymphocytes (>50%) and the percentage of cells expressing skin-homing receptor (cutaneous lymphocyte-associated antigen) (>70%) and chemokine receptors (CCR4 and CXCR3) at T1. A positive proliferative response was observed in T lymphocytes (stimulation index [SI] = 3.5 in patient 1 and 3.59 in patient 2), especially the CD8(+) subpopulation (SI = 5.5 and 4.6 in patients 1 and 2, respectively), and NK lymphocytes (SI = 3.9 and 8.5 in patients 1 and 2, respectively) after glatiramer acetate stimulation.

CONCLUSION:

This study demonstrates the important role of T(H)1 cells expressing skin-homing receptors in delayed-type hypersensitivity reactions to glatiramer acetate. A lymphocyte transformation test revealed a specific glatiramer acetate recognition by T lymphocytes and NK lymphocytes.

• Authors: Cristobalina Mayorga, Ana B Blazquez, Inmaculada Doña, Francisca Gomez, Patricia Chaves, Maria J Sanchez-Quintero, Natalia Blanca-López, Lidia Melendez, Miguel Blanca, Maria Jose Torres
• Journal: Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (Ann Allergy Asthma Immunol) Vol. 109 Issue 1 Pg. 47-51 (Jul 2012) ISSN: 1534-4436 [Electronic] United States
• PMID: 22727157 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antigens, Differentiation, T-Lymphocyte
• CCR4 protein, human
• CTAGE1 protein, human
• CXCR3 protein, human
• Immunosuppressive Agents
• Membrane Glycoproteins
• Peptides
• Receptors, CCR4
• Receptors, CXCR3
• Glatiramer Acetate

Topics

• Adult
• Antigens, Differentiation, T-Lymphocyte (blood, immunology)
• CD8-Positive T-Lymphocytes (immunology, metabolism)
• Drug Hypersensitivity (diagnosis, immunology)
• Exanthema (diagnosis, immunology)
• Female
• Flow Cytometry
• Glatiramer Acetate
• Humans
• Hypersensitivity, Delayed (diagnosis, immunology)
• Immunosuppressive Agents (administration & dosage, adverse effects)
• Intradermal Tests (methods)
• Killer Cells, Natural (immunology, metabolism)
• Lymphocyte Activation (immunology)
• Membrane Glycoproteins (blood, immunology)
• Middle Aged
• Multiple Sclerosis (drug therapy)
• Peptides (administration & dosage, adverse effects)
• Receptors, CCR4 (blood, immunology)
• Receptors, CXCR3 (blood, immunology)
• Skin Tests
• Th1 Cells (immunology, metabolism)