Abstract：
A close association between hereditary alpha-tryptasemia (HAT) and mast cell (MC) disorders has been previously reported. However, the relationship between HAT and the diagnostic subtypes and clinical features of MC disorders still remains to be established.
To determine the prevalence of HAT in healthy donors (HD) vs patients with different diagnostic subtypes of MC activation syndromes (MCAS) and mastocytosis, and its relationship with the clinical behavior of the disease.
A total of 959 subjects were studied including 346 healthy donors (HD), 464 mastocytosis, and 149 non-clonal MCAS patients. Molecular studies to assess the TPSAB1 genotype were performed, and data on serum baseline tryptase (sBT) and basal MC-mediator release episodes and triggers of anaphylaxis were collected.
HAT was detected in 15/346 (4%) HD versus 43/149 (29%) non-clonal MCAS and 84/464 (18%) mastocytosis cases. Among mastocytosis, HAT was more frequently found in patients with MC-restricted KITD816V (21% vs. 10% among multilineage KITD816V patients; p = .008). Overall, median sBT was higher in cases presenting with HAT (28.9 vs. 24.5 ng/mL; p = .008), while no significant differences in sBT were observed among HAT+ mastocytosis patients depending on the presence of 1 vs. ≥2 extra copies of the α-tryptase gene (44.1 vs. 35.2 ng/mL, p > .05). In turn, anaphylaxis was more frequently observed in HAT+ versus HAT- mastocytosis patients (76% vs. 65%; p = .018), while HAT+ and HAT- patients who did not refer anaphylaxis as the presenting symptom (n = 308) showed a similar prevalence of subsequent anaphylaxis (35% vs. 36%, respectively).
The frequency of HAT in MC disorders varies according to the diagnostic subtype of the disease. HAT does not imply a higher risk (and severity) of anaphylaxis in mastocytosis patients in whom anaphylaxis is not part of the presenting symptoms of the disease.
To determine the prevalence of HAT in healthy donors (HD) vs patients with different diagnostic subtypes of MC activation syndromes (MCAS) and mastocytosis, and its relationship with the clinical behavior of the disease.
A total of 959 subjects were studied including 346 healthy donors (HD), 464 mastocytosis, and 149 non-clonal MCAS patients. Molecular studies to assess the TPSAB1 genotype were performed, and data on serum baseline tryptase (sBT) and basal MC-mediator release episodes and triggers of anaphylaxis were collected.
HAT was detected in 15/346 (4%) HD versus 43/149 (29%) non-clonal MCAS and 84/464 (18%) mastocytosis cases. Among mastocytosis, HAT was more frequently found in patients with MC-restricted KITD816V (21% vs. 10% among multilineage KITD816V patients; p = .008). Overall, median sBT was higher in cases presenting with HAT (28.9 vs. 24.5 ng/mL; p = .008), while no significant differences in sBT were observed among HAT+ mastocytosis patients depending on the presence of 1 vs. ≥2 extra copies of the α-tryptase gene (44.1 vs. 35.2 ng/mL, p > .05). In turn, anaphylaxis was more frequently observed in HAT+ versus HAT- mastocytosis patients (76% vs. 65%; p = .018), while HAT+ and HAT- patients who did not refer anaphylaxis as the presenting symptom (n = 308) showed a similar prevalence of subsequent anaphylaxis (35% vs. 36%, respectively).
The frequency of HAT in MC disorders varies according to the diagnostic subtype of the disease. HAT does not imply a higher risk (and severity) of anaphylaxis in mastocytosis patients in whom anaphylaxis is not part of the presenting symptoms of the disease.
摘要：
背景：先前已经报道了遗传性α-色胺血症（HAT）和肥大细胞（MC）疾病之间的密切关系。然而,HAT与MC疾病的诊断亚型和临床特征之间的关系仍有待确定。
目的：为了确定健康供体（HD）与具有不同诊断亚型MC激活综合征（MCAS）和肥大细胞增多症的患者中HAT的患病率，及其与疾病临床行为的关系。
方法：共研究了959名受试者，包括346名健康捐献者（HD），464个肥大细胞增多症,149例非克隆MCAS患者。进行了评估TPSAB1基因型的分子研究，收集血清基线类胰蛋白酶（sBT）和基础MC介质释放发作和过敏反应触发因素的数据。
结果：在15/346（4％）HD与43/149（29％）非克隆MCAS和84/464（18％）肥大细胞增多病例中检测到HAT。在肥大细胞增多症中,在MC限制性KITD816V患者中发现HAT更为常见(21%vs.多谱系KITD816V患者中的10%；p=.008)。总的来说,出现HAT的病例中sBT中位数较高(28.9vs.24.5ng/mL；p=.008），虽然在HAT+肥大细胞增多症患者中观察到sBT没有显着差异，这取决于1与α-类胰蛋白酶基因的≥2个额外拷贝（44.1与35.2ng/mL,p>.05）。反过来,在HAT+与HAT-肥大细胞增生症患者中更频繁观察到过敏反应(76%与65%；p=.018），而HAT+和HAT-没有将过敏反应作为表现症状的患者（n=308）表现出类似的后续过敏反应患病率（35％vs.36%,分别)。
结论：在MC疾病中HAT的频率根据疾病的诊断亚型而变化。在肥大细胞增多症患者中，HAT并不意味着过敏反应的风险（和严重程度）更高。
目的：为了确定健康供体（HD）与具有不同诊断亚型MC激活综合征（MCAS）和肥大细胞增多症的患者中HAT的患病率，及其与疾病临床行为的关系。
方法：共研究了959名受试者，包括346名健康捐献者（HD），464个肥大细胞增多症,149例非克隆MCAS患者。进行了评估TPSAB1基因型的分子研究，收集血清基线类胰蛋白酶（sBT）和基础MC介质释放发作和过敏反应触发因素的数据。
结果：在15/346（4％）HD与43/149（29％）非克隆MCAS和84/464（18％）肥大细胞增多病例中检测到HAT。在肥大细胞增多症中,在MC限制性KITD816V患者中发现HAT更为常见(21%vs.多谱系KITD816V患者中的10%；p=.008)。总的来说,出现HAT的病例中sBT中位数较高(28.9vs.24.5ng/mL；p=.008），虽然在HAT+肥大细胞增多症患者中观察到sBT没有显着差异，这取决于1与α-类胰蛋白酶基因的≥2个额外拷贝（44.1与35.2ng/mL,p>.05）。反过来,在HAT+与HAT-肥大细胞增生症患者中更频繁观察到过敏反应(76%与65%；p=.018），而HAT+和HAT-没有将过敏反应作为表现症状的患者（n=308）表现出类似的后续过敏反应患病率（35％vs.36%,分别)。
结论：在MC疾病中HAT的频率根据疾病的诊断亚型而变化。在肥大细胞增多症患者中，HAT并不意味着过敏反应的风险（和严重程度）更高。
