Co-occurrence of IgE and IgG autoantibodies in patients with chronic spontaneous urticaria

Abstract

Chronic spontaneous urticaria (CSU) pathogenesis shows a complex and still unclear interplay between immunoglobulin (Ig)G-and IgE-mediated autoimmunity, leading to mast cell and basophil degranulation and wheal formation. The objective of this study was to evaluate at the same time IgE-and IgG-reactivity to well recognized and recently reported autoantigens in CSU patients, and to assess the effects of such reactivity on response to the anti-IgE monoclonal antibody omalizumab. Twenty CSU patients underwent omalizumab treatment. Urticaria activity score 7 (UAS7) was recorded at baseline and at different drug administration time-points for categorizing early-, late-or non-responders. At baseline, sera from the 20 patients and from 20 controls were tested for IgE and IgG autoantibodies to high-and low-affinity IgE receptors (FcεRI and FcεRII), tissue factor (TF) and thyroglobulin (TG) by immunoenzymatic methods. Antibody levels were compared with those of controls and analysed according to response. Eighteen patients were omalizumab responders (11 early and seven late), while two were non-responders. More than 50% of patients had contemporary IgE and IgG to at least to one of the four different autoantigens. Late responders showed higher levels of both anti-TF IgE and IgG than early responders (P = 0·011 and P = 0·035, respectively). Twenty-five per cent of patients had levels of anti-FcεRI IgE, exceeding the upper normal limit, suggesting that it could be a novel auto-allergen in CSU. In CSU, there is an autoimmune milieu characterized by the co-existence of IgE and IgG autoantibodies to the same antigen/allergen, particularly in late responders to omalizumab, possibly explaining the slower response.

Clinical variables of severe chronic spontaneous urticaria from total IgE standpoint: a retrospective study

“…Altogether, importantly, this study shows that CSU patients show in most cases a mixed clinical picture where signs of atopic status co-exist with signs of an autoimmune disease. In effect, in previous studies (4) only a small minority of CSU patients showed a clear-cut IgG-mediated autoimmune picture based on three distinct parameters suggesting that in most cases the pathogenesis probably is a mixed one (8).…”

Autoimmune Diseases Are Linked to Type IIb Autoimmune Chronic Spontaneous Urticaria

“…Importantly, such studies need to also compare patients with type I and type IIb autoimmune CSU with patients who have both type I and type IIb autoimmune CSU, a subpopulation of CSU patients that is currently ill characterized in terms of its rate and clinical characteristics. 51 In addition, the 3 markers for aiCSU, i.e. basophils tests, ASST and IgG anti-FcεRIα/IgE, were only analyzed, in combination, in the patients from the PURIST study.…”

Chronic spontaneous urticaria treated with Omalizumab: what differentiates early from late responders

“…In patients showing a slow response to omalizumab it is possible that this latter mechanism of action is the most important. In effect, a very recent study seems to suggest that the contemporary presence of IgE and IgG-mediated autoimmunity (particularly against the high affinity IgE receptor) may slow down the clinical response to the drug (12).…”