Direct versus sequential immunoglobulin switch in allergy and antiviral responses

• The onset of HDM or A. alternata allergy is manifested almost exclusively by the increase in specific IgE.
• These results are consistent with a direct mu to epsilon CSR in allergy.
• Antiviral response is characterized by IgG production with minor input of IgA and IgG4.
• Antiviral response is characterized by dominant direct mu to gamma switch.
• Sequential switches to IgA1, IgG4 and IgA2 do occur but represent rare events even in anti-EBV response.

Allergy is characterized by IgE production to innocuous antigens. The question whether the switch to IgE synthesis occurs via direct or sequential pathways is still unresolved. The aim of this work was to analyze the distribution of immunoglobulins (Ig) to house dust mite D. farinae and A. alternata fungus in allergic children with primarily established diagnosis and compare it to Epstein-Barr antiviral (EBV) response in the same patients. In allergy patients the only significant difference was found in allergen specific IgE, likely mediated by a direct isotype switch, while antiviral response was dominated by EBV specific IgG and low level of concordant IgA and IgG4 production consistent with a minor sequential Ig switches. Taken collectively, we concluded that sequential isotype switch is likely to be a much rarer event than a direct one.