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Autoimmune Urticaria:Immunological Markers J Investig Allergol Clin Immunol 2011;Vol.21(7):546-550 2011 Esmon PublicidadORIGINAL ARTICLEChronic Autoimmune Urticaria:Frequency and Association With Immunological MarkersM Abd El-Azim,S Abd El-AzimMedical Microbiology and Immunology,Faculty of Medicine,Zagazig University,Zagazig,Egypt AbstractBackground:Chronic autoimmune urticaria(CAU),a subgroup of chronic idiopathic urticaria(CIU),is characterized by severe and persistent wheals accompanied by redness and itching.Diagnosis is almost completely based on clinical suspicion and the results of the autologous serum skin test(ASST).Objectives:To determine the frequency of CAU and compare the clinical and laboratory parameters of patients with positive and negative ASST results.Patients and Methods:A total of 165 patients with chronic urticaria(CU)were enrolled;31 were excluded(known causes and pregnancy/breastfeeding),leaving 134 patients with CIU.A clinical evaluation and routine and specifi c laboratory tests were performed.Results:The cause of CU was identifi ed in 18.9%of patients;81.2%patients were considered to have CIU.The ASST result was positive in 39.6%of patients with CIU,who had more frequent urticaria attacks than patients with a negative ASST result.Patients with positive results had a higher urticaria activity score than those with negative results,although the difference was not statistically signifi cant.As for immunological markers,the absolute eosinophil count and serum immunoglobulin(Ig)E titer were lower in patients with a positive ASST result than in those with a negative ASST result,although,again,the difference was not statistically signifi cant(P=.07).Antithyroid antibody titer and B-cell percentage were higher in patients with a positive ASST result than in those with a negative result,and the difference was statistically signifi cant(P=.04 and.004,respectively).Conclusions:ASST remains a baseline diagnostic test for CAU.Patients with CAU had more frequent attacks and higher antithyroid antibody titers and peripheral B-cell percentages,as well as lower absolute eosinophil counts and serum IgE concentrations.Key words:Autologous serum skin test.Chronic urticaria.Autoimmunity.ResumenAntecedentes:La urticaria crnica autoinmunitaria(UCA),un subgrupo de urticaria crnica idioptica(UCI),se caracteriza por la presencia de habones de carcter grave y persistente acompaados de enrojecimiento y prurito.El diagnstico se basa casi por completo en la sospecha clnica y los resultados de la prueba cutnea con suero autlogo(PCSA).Objetivos:Determinar la frecuencia de la UCA y comparar los parmetros clnicos y de laboratorio de pacientes con resultados positivos y negativos en la PCSA.Pacientes y mtodos:Se incluy a 165 pacientes con urticaria crnica(UC),de los que se excluy a 31(causas conocidas y embarazo/lactancia),quedando 134 pacientes con UCI.Se llevaron a cabo una evaluacin clnica y anlisis de rutina y especfi cos.Resultados:La causa de la UC se identifi c en un 18,9%de los pacientes;se consider que un 81,2%de pacientes padeca UCI.El resultado de la PCSA fue positivo en un 39,6%de pacientes con UCI,que tenan episodios de urticaria con mayor frecuencia que los pacientes con un resultado negativo en la PCSA.Los pacientes con resultados positivos presentaron una puntuacin de actividad de urticaria ms elevada que aquellos con resultados negativos,si bien la diferencia no fue estadsticamente signifi cativa.En cuanto a los marcadores inmunolgicos,el recuento absoluto de eosinfi los y el ttulo de inmunoglobulina(Ig)E en suero fueron ms bajos en pacientes con un resultado positivo en la PCSA que en aquellos con un resultado negativo en dicha prueba,aunque,de nuevo,la diferencia no fue estadsticamente signifi cativa(p=0,07).El ttulo de anticuerpos antitiroideos y el porcentaje de linfocitos B fueron mayores en los pacientes con un resultado positivo en la PCSA que en aquellos con un resultado negativo,y la diferencia fue estadsticamente signifi cativa(p=0,04 y 0,004,respectivamente).Conclusiones:La PCSA sigue siendo una prueba diagnstica bsica para la UCA.Los pacientes con UCA presentaron episodios ms frecuentes,ttulos de anticuerpos antitiroideos y porcentajes de linfocitos B perifricos ms elevados,as como recuentos absolutos de eosinfi los y concentraciones sricas de IgE ms bajos.Palabras clave:Prueba cutnea con suero autlogo.Urticaria crnica.Autoinmunidad.J Investig Allergol Clin Immunol 2011;Vol.21(7):546-550 2011 Esmon PublicidadM Abd El-Azim,et al547IntroductionChronic urticaria(CU)is a common skin disorder,affecting 0.1%-1%of the general population.It is characterized by recurrent and transitory(5%or 350 cells/mm3 18.3.Serum total IgE level(Immundiagnostik IgE ELISA kit,Immundiagnostik AG,Bensheim,Germany).4.Antithyroid peroxidase(anti-TPO)antibody(Medizym anti-TPO ELISA,Medipan Diagnostica,Dahlewitz/Berlin,Germany).All the procedures were performed according to the manufacturers instructions.Anti-TPO antibody values of 30 IU/mL were considered positive.5.Flow cytometry.The percentage of CD3 CD19+B lymphocytes in peripheral blood was detected.Two-color analysis was performed using monoclonal antibodies marked with CD19-fl uorescein isothiocyanate(HIB19 clone;BD Pharmingen,San Diego,California,USA)and CD3-allophycocyanin(UCHT1clone;BD PharMingen)according to the manufacturers instructions.Cells were analyzed using a FACScan fl ow cytometer(Becton Dickinson,San Diego,California,USA)and CellQuest software(Becton Dickinson,Mountainview,California,USA).6.ASST technique.Patients received an intradermal injection(50 L of autologous serum,histamine diphosphate,and sterile physiological saline)into the volar forearm 15,19,avoiding areas known to have had spontaneous wheals in the previous 48 hours(mast cells may be refractory to further activation local tachyphylaxis)20.After 30 minutes(15 minutes for histamine),the wheal was measured at its 2 longest perpendicular diameters and the average was calculated 6.A positive ASST result was defi ned as a serum-induced wheal with a diameter of 1.5 mm as compared to a saline-induced wheal at 30 minutes(Figure).Autoimmune Urticaria:Immunological Markers J Investig Allergol Clin Immunol 2011;Vol.21(7):546-550 2011 Esmon Publicidad548Figure.A positive result in the autologous serum skin test.Serum was injected more proximally and histamine more distally,with normal saline in the middle.A signifi cant wheal and fl are response was seen at the serum and histamine injection sites only.The diameter of the serum-induced wheal is 1.7 mm greater than that of the saline-induced wheal.Statistical AnalysisData were recorded and processed using SPSS version 12.0(SPSS Inc.,Chicago,Illinois,USA).Quantitative variables were expressed as mean(SD)and compared using the Mann-Whitney test for 2 independent variables.Qualitative variables were expressed as frequency and percentage and compared using the 2 test or Fisher exact test when appropriate.A P value 5/wk,No.(%)49(92.5%)52(52.8%)5 times/week)was signifi cantly greater in the positive group than in the negative group(P5 times/week)were signifi cantly more common in ASST-positive patients than in ASST-negative patients.This fi nding was consistent with the results of George et al and could be explained by the diffi culty in controlling CAU.Our study showed that the severity of urticaria was greater,although not signifi cantly so,if the ASST result was positive.This is consistent with the fi ndings of Bajaj et al 17.However,Caproni et al 21 found that patients with a positive ASST result presented more severe clinical features than those with a negative result.As for immunological markers,absolute eosinophil count was not signifi cantly lower in patients with a positive ASST result,although it was within the upper limits of normal.This reduction is consistent with the accumulation of eosinophils in lesional skin 28:eosinophils are recruited following the release of cytokines and chemotactic factors and activation and recruitment of adhesion molecules on migrating eosinophils and on endothelial cells 29.The role of tissue eosinophilia is unclear,although it is possible that release of toxic major basic protein and eosinophil cationic protein further augments histamine release from mast cells in the late phase of the urticarial wheal 9.We found that a positive ASST result was more likely to be associated with signifi cantly lower IgE levels than ASST-negative patients.This fi nding agrees with those of Huilan et al 5,who attributed this association to IgEanti-IgE immune complex formation that reduces the amount of detectable free IgE in patients with anti-IgE autoantibodies.In contrast,other authors showed serum IgE level to be signifi cantly higher in ASST-positive patients 6,30,and this could be due to an improvement in CAU patients after treatment with the anti-IgE antibody omalizumab,which selectively binds to IgE,thus decreasing IgE receptor density on basophils and cutaneous mast cells and preventing activation by autoantibodies 6.The signifi cant association between a positive ASST result and anti-TPO antibody titer is consistent with the fi ndings of other studies and can be explained by segregation of anti-TPO antibodies from IgE receptor antibodies because of B-cell hyperreactivity 23,31.However,other authors did not detect a difference in the incidence of thyroid disease,probably as a result of insuffi cient sample size(thyroid autoimmunity occurs in less than 6%of the general population)32.Finally,we found that ASST-positive CAU patients were more likely to be associated with a higher percentage of B cells.This fi nding agrees with those of Huilan et al 5 and Toubi et al 33,who reported increased proliferation rates and decreased apoptosis rates for B cells.In conclusion,ASST is a baseline diagnostic test for CAU.Patients with CAU have more frequent attacks and higher anti-TPO antibody titers and peripheral B-cell percentages,as well as lower absolute blood eosinophil counts and serum IgE titers.Thyroid function and anti-TPO antibody titers should be routinely assessed in CU patients.In addition,successful therapy for urticaria should target the regulatory pathway linking B cells and IgE in order to downregulate FcRI expression.References 1.Greaves MW,Tan KT.Chronic urticaria:recent advances.Clin Rev Allergy Immunol.2007;33:134-43.2.Ferrer M,Kinet,JP,and Kaplan AP.Comparative studies of functional and binding assays for IgG anti-FceRI(-subunit)in chronic urticaria.J Allergy Clin Immunol.1998;101:672-6.3.Platzer MH,Grattan CEH,Poulsen LK,Skov PS.Validation of basophil histamine release against the autologous serum skin test and outcome of serum-induced basophil histamine release studies in a large population of chronic urticaria patients.Allergy.2005;60:1152-6.4.Schocket AL.Chronic urticaria:pathophysiology and etiology,or the what and why.Allergy Asthma 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