Biomarkers of Autoimmune Chronic Spontaneous Urticaria.

PURPOSEOF REVIEW: Chronic spontaneous urticaria and chronic inducible urticaria (CSU/CindU) are caused by mast cell and basophil activation leading to degranulation and the release of histamine and several other mediators. Three kinds of factors can trigger mast cells in CSU: (1) activation of stimulating receptor(s) on the mast cell membrane, (2) upregulation of certain receptor(s), and (3) intracellular dysregulation in signaling with overexpression of the spleen tyrosine kinase (SYK) or reduced activation of the inhibitory Src homology 2 (SH2)-containing inositol phosphatases (SHIP)-related pathways. In CSU, two major endotypes exist based on the primary receptor activating mechanism: type I hypersensitivity (IgE-mediated, directed against auto-allergens) and type IIb (autoimmune, via IgG autoantibodies directed against IgE or the IgE-receptor). Their treatment responses vary. We discuss in vitro and in vivo biomarkers. RECENT FINDINGS: Patients with auto-allergic CSU have clinical characteristics that can distinguish them partly from those with autoimmune CSU. Most importantly, their disease generally presents a less aggressive course, a better response to second generation (up-dosed) antihistamines and a good response to omalizumab, if necessary. Meanwhile, autoimmune CSU/CindU patients fare less well and often need immunosuppressive drugs. Biomarkers that might help endotype CSU/CindU patients and select the most appropriate treatment, dose, and duration, e.g., for autoallergic CSU, high total IgE and IgE against auto-allergens; for autoimmune CSU, low IgE, basopenia, and IgG against autoantigens like thyroid peroxidase and a positive autologous serum skin test (but sometimes also positive in autoallergy). Some biomarkers are easily accessible but of low specificity; others are highly specific but more futuristic.

Decreased serum levels of IL-27and IL-35 in patients with Graves disease.

OBJECTIVE: Graves' disease (GD) is an autoimmune disease causing the overproduction of the thyroid hormone from thyroid gland. This disease is mainly the result of the production of antibodies against TSH receptors. Cytokines play an important role in orchestrating the pathophysiology in autoimmune thyroid disease. The regulatory role of IL-12 on TH1 cells has been proven. IL-27 and IL-35, members of IL-12 cytokine family, are two cytokines that have been newly discovered. IL-35 has been identified as a novel immunosuppressive and anti-inflammatory cytokine while IL-27 has both inflammatory and anti-inflammatory functions. The objective of the current study was to examine the changes in the serum level of the foregoing cytokines in GD patients in comparison to healthy controls. METHODS: In this study, serum levels of IL-27 and IL-35 were determined by an ELISA method; anti TPO and anti Tg were measured by an RIA method in 40 new cases of Graves's disease. The findings were compared with 40 healthy controls. RESULTS: The results showed a significant difference between IL-27 and IL-35 regarding their serum levels with P values of 0.0001 and 0.024, respectively; anti TPO and anti Tg levels of the cases were also significantly different from controls (p < 0.001). CONCLUSION: The reduction in the serum levels of IL-27 and IL-35 in GD patients compared to normal subjects suggests the possible anti-inflammatory role of these cytokines in GD.

Decreased serum levels of IL-27and IL-35 in patients with Graves disease

ABSTRACT Objectives Graves' disease (GD) is an autoimmune disease causing the overproduction of the thyroid hormone from thyroid gland. This disease is mainly the result of the production of antibodies against TSH receptors. Cytokines play an important role in orchestrating the pathophysiology in autoimmune thyroid disease. The regulatory role of IL-12 on TH1 cells has been proven. IL-27 and IL-35, members of IL-12 cytokine family, are two cytokines that have been newly discovered. IL-35 has been identified as a novel immunosuppressive and anti-inflammatory cytokine while IL-27 has both inflammatory and anti-inflammatory functions. The objective of the current study was to examine the changes in the serum level of the foregoing cytokines in GD patients in comparison to healthy controls. Materials and methods In this study, serum levels of IL-27 and IL-35 were determined by an ELISA method; anti TPO and anti Tg were measured by an RIA method in 40 new cases of Graves's disease. The findings were compared with 40 healthy controls. Results The results showed a significant difference between IL-27 and IL-35 regarding their serum levels with P values of 0.0001 and 0.024, respectively; anti TPO and anti Tg levels of the cases were also significantly different from controls (p < 0.001). Conclusion The reduction in the serum levels of IL-27 and IL-35 in GD patients compared to normal subjects suggests the possible anti-inflammatory role of these cytokines in GD.

Autoinmunidad y función tiroidea en escolares de 2 regiones del Estado Mérida con deficiencia de yodo corregida

Objetivos: El presente estudio transversal fue planificado para evaluar la presencia de anticuerpo antitiroideo antiperoxidasa (ac.anti-TPO) y la función tiroidea, en dos áreas endémicas de bocio, con deficiencia de yodo corregida. Métodos: Se estudiaron 109 escolares, de ambos sexos, entre 6-12 años de edad, procedentes de Bailadores (BA=54) y Mucuchíes (MU=55). El diagnóstico de bocio se obtuvo por palpación clínica. La yoduria se determinó en 34 niños de BA y en 37 de MU, mientras que la concentración sérica de T4 libre (T4L), T3 libre (T3L), T3 total (T3T), TSH y ac.anti-TPO fueron determinadas en todos los escolares estudiados. Adicionalmente se realizó la cuantificación de T3T y ac.anti-TPO en uno de los progenitores de cada niño. Resultados: En BA, el 53,5% de los escolares presentaron bocio y en MU el 42,5%. La mediana de la excreción urinaria de yodo no fue estadísticamente diferente entre ambos grupos (BA=181 µg/L, MU=200 µg/L). La frecuencia global de detectabilidad de ac.anti-TPO en escolares fue del 45,5%, pero solo el 5% presentó seropositivad. Una concentración de ac. anti-TPO, entre 10 y 30 UI/mL, se observó en el 39% de los niños de BA y 40% en MU; 87% en adultos de BA y 54% en MU. En BA, concentraciones de ac.anti-TPO mayores de 30 UI/mL se observaron en el 10% de los niños y en el 17% de los adultos; en MU, no se observó ningún caso positivo para ac.anti-TPO en niños, mientras que en adultos la frecuencia de positividad fue del 8%. Las pruebas de función tiroidea de los escolares y de los progenitores de ambas regiones fueron similares y compatibles con estado de eufunción No hubo asociación entre la presencia de ac.anti-TPO y bocio. Conclusiones: Estos resultados indican que la corrección de la deficiencia de yodo en las áreas endémicas estudiadas se asocia con una alta frecuencia de detectabilidad de ac.anti-TPO, sin cambios en la función tiroidea.

Objective: This cross-sectional study was designed to evaluate the thyroid peroxidase autoantibody (TPO-Ab) concentrations and thyroid function in schoolchildren from two geographic regions were iodine deficiency was corrected. Methods: One hundred nine schoolchildren 6 to 12 years of age were studied: Bailadores (BA=54) and Mucuchíes (MU=55). Goiter size, urinary iodine, and serum freeT4, freeT3, total T3, TSH and TPO-Ab were measured. Total T3 and TPO-Ab were also determined in some parents. Results: Overall frequency of TPO-Ab detectability and positivity in schoolchildren were 45,5% and 5% respectively. TPO-Ab concentration ranging between 10-30 UI/mL was observed in 39% of children from BA and 40% from MU; 87% of parents from BA and 54% from MU. TPO-Ab concentration >30 UI/mL was observed in 10% of children and 17% of their parents. None of the children from MU had positive TPO-Ab, while 8% of their parents were positive. Median urinary iodine was similar in both regions (BA=181 µg/L, MU=200 µg/L). Thyroid function tests were normal in all cases. Goiter was found in 53,5% of children from BA and 42,5% from MU . No association between goiter and ac.TPO-Ab concentration was observed. Conclusions: These results suggest that in both endemic goiter regions, sufficient iodine prophylaxis by iodized salt is frequently associated with low detectable TPO-Ab levels and no changes in thyroid function.