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


CONCLUSIONS
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.
Pediatrics Service, Carlos Haya Hospital, Malaga, Spain.
Cristobalina
C
Mayorga
Ana B
AB
Blazquez
Inmaculada
I
Doña
Francisca
F
Gomez
Patricia
P
Chaves
Maria J
MJ
Sanchez-Quintero
Natalia
N
Blanca-López
Lidia
L
Melendez
Miguel
M
Blanca
Maria Jose
MJ
Torres
D000328:Adult; D000945:Antigens, Differentiation, T-Lymphocyte / Q000097:blood / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D004342:Drug Hypersensitivity / Q000175:diagnosis / Q000276:immunology*; D005076:Exanthema / Q000175:diagnosis / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D000068717:Glatiramer Acetate; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000175:diagnosis / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D007428:Intradermal Tests / Q000379:methods; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000097:blood / Q000276:immunology; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy*; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects*; D054398:Receptors, CCR4 / Q000097:blood / Q000276:immunology; D054367:Receptors, CXCR3 / Q000097:blood / Q000276:immunology; D012882:Skin Tests; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
D000945:Antigens, Differentiation, T-Lymphocyte; C515354:CCR4 protein, human; C063419:CTAGE1 protein, human; C515187:CXCR3 protein, human; D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; D010455:Peptides; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D000068717:Glatiramer Acetate