Influence of neutralizing antibodies to adalimumab and infliximab on the treatment of psoriasis.

BACKGROUND: Current treatment with biologics has produced dramatic therapeutic effects in patients with psoriasis, although these agents occasionally decrease in efficacy. One of the main factors responsible for this attenuation is attributed to the development of antidrug antibodies (ADAs). OBJECTIVES: To analyse the relationship between serum drug concentrations, the presence of ADAs and treatment efficacy of adalimumab and infliximab, and to determine the optimal use of these biologics. METHODS: This was a 1-year prospective study in the dermatology departments of Kobe University Hospital and collaborating hospitals. All patients starting a regimen of adalimumab and infliximab for psoriasis were included. We measured the serum concentration of the drugs and titres of antibodies to adalimumab and infliximab, as well as the Psoriasis Area and Severity Index scores at weeks 0, 4, 12, 24 and 48 during the first year of treatment. RESULTS: We observed a 50% positive rate of ADAs to adalimumab, and a 41% positive rate of ADAs to infliximab. The titres of ADAs showed a wide range from low to high titres. In the high-titre groups, the patients exhibited a decreased clinical response, and demonstrated a negative correlation between titre and clinical response. However, an equivalent therapeutic effect was observed between the low-titre group and the group with no antibodies detected for adalimumab. For infliximab, the patients with ADAs showed decreased clinical response. An apparent negative correlation between antibody production and reduced clinical response was observed. CONCLUSIONS: Two biologics, adalimumab and infliximab, showed different therapeutic behaviour. The measurement of ADAs and drug concentrations has important implications for treatment with biologics.

Soybean beta-conglycinin as the main allergen in a patient with food-dependent exercise-induced anaphylaxis by tofu: food processing alters pepsin resistance.

BACKGROUND: Food-dependent exercise-induced anaphylaxis (FDEIA) due to soybeans is a rare disorder. The allergen responsible for FDEIA due to soybeans has not yet been determined. OBJECTIVE: We characterized the clinical features of a patient with FDEIA due to tofu, who was well tolerant to drinking soy milk. We then sought to identify the responsible soybean allergen(s) in that patient. We further studied whether different stabilities of the allergen(s) to pepsin digestion between two soybean products are related to their clinical allergenicity. METHODS: Skin prick tests and provocation tests using soybean products were performed to detect the responsible food and other factors that induced the allergic symptoms. Specific IgE to various soybean allergens were examined by ImmunoCAP, ELISA and protein microarray assays. Immunoblotting for soybeans and soybean products using the patient's serum was also performed. Soybean products were serially digested by pepsin to disclose the stability of the allergens. RESULTS: Provocation with ingestion of tofu and exercise induced the allergic symptoms, while ingestion of soy milk and exercise did not. Immunoblot analysis, ELISA and protein microarray assay revealed that beta-conglycinin mainly reacts with IgE antibodies in the patient's serum. By immunoblot analysis, beta-conglycinin in soy milk completely disappeared after pepsin digestion within 20 min, whereas beta-conglycinin in tofu was almost intact after more than 120 min of pepsin digestion. CONCLUSION: We identified beta-conglycinin as the causative allergen in a patient with FDEIA induced by tofu. The difference in resistance to pepsin digestion between tofu and soy milk suggests that the presence of undigested allergens in the digestive tract is a prerequisite for the development of FDEIA.