Immunological Study of Non Immediate Allergic Reaction to Infliximab

RATIONALE: Infliximab is a chimeric monoclonal antibody against TNF-α extensively employed in the therapy of rheumatoid arthritis. Hypersensitivity reactions to this drug, both acute and delayed infusion reactions have been described. Cutaneous delayed hypersensitivity reactions are rare, and the underlying pathomechanisms have not been studied and a T cell involvement has not been achieved. We present two patients with delayed skin eruptions after infliximab administration where a T-cell mechanism has been demonstrated.METHODS: The allergological study consisted of patch testing and drug provocation test (DPT) with infliximab at increases doses. The immunological monitorization of the response (T1, T2 and basal) included cellular marker analysis by flow cytometry, skin biopsy and lymphocyte transformation test (LTT)RESULTS: The patch testing were negative with infliximab at 48-72 hours reading in both patients. After DPT with infliximab a maculopapular exanthema was developed in the two patients 24 and 30 hours respectively. The immunological study showed an increase of CD3+CD4+ lymphocytes with high expression of CXCR3, CLA and CCR10. We observed a strong increase of perforin in both T and NK lymphocytes. These results were confirmed in the skin biopsy obtained after DPT. The LTT showed a CD3+-T-lymphocyte proliferation after infliximab stimulation in the two patients being negative in 10 tolerant controls.CONCLUSIONS: These cases indicate that delayed hypersensitivity reactions to infliximab do exist. The monitorization of the immunological response showed T-lymphocyte involvement with skin homing and a Th1 pattern with cytotoxic characteristics. RATIONALE: Infliximab is a chimeric monoclonal antibody against TNF-α extensively employed in the therapy of rheumatoid arthritis. Hypersensitivity reactions to this drug, both acute and delayed infusion reactions have been described. Cutaneous delayed hypersensitivity reactions are rare, and the underlying pathomechanisms have not been studied and a T cell involvement has not been achieved. We present two patients with delayed skin eruptions after infliximab administration where a T-cell mechanism has been demonstrated. METHODS: The allergological study consisted of patch testing and drug provocation test (DPT) with infliximab at increases doses. The immunological monitorization of the response (T1, T2 and basal) included cellular marker analysis by flow cytometry, skin biopsy and lymphocyte transformation test (LTT) RESULTS: The patch testing were negative with infliximab at 48-72 hours reading in both patients. After DPT with infliximab a maculopapular exanthema was developed in the two patients 24 and 30 hours respectively. The immunological study showed an increase of CD3+CD4+ lymphocytes with high expression of CXCR3, CLA and CCR10. We observed a strong increase of perforin in both T and NK lymphocytes. These results were confirmed in the skin biopsy obtained after DPT. The LTT showed a CD3+-T-lymphocyte proliferation after infliximab stimulation in the two patients being negative in 10 tolerant controls. CONCLUSIONS: These cases indicate that delayed hypersensitivity reactions to infliximab do exist. The monitorization of the immunological response showed T-lymphocyte involvement with skin homing and a Th1 pattern with cytotoxic characteristics.