The diagnosis of histoplasmosis depends on various approaches: direct clinical examination, fungus isolation from cultures of clinical samples, histopathological evaluation, and serological testing. In serodiagnostic assays, the Histoplasma capsulatum H and M antigenic glycoproteins have been extensively used. However, both antigens showed limitations attributed mainly to their cross-reactivity with glycoproteins from other pathogenic fungi, which compromises specificity, and generates false positives, misdiagnosis, and therapeutic failure. In this work, we deglycosylated extracellular released antigens from the Venezuelan 7090 H. capsulatum clinical isolate, using chemical and enzymatic methods and evaluated their effectiveness by indirect enzyme-linked immunosorbent assay (ELISA) with sera from patients with either histoplasmosis or PCM. Prior to deglycosylation, the extracellular released antigen showed 62% of sensitivity 66% of specificity and 68% of cross-reactivity with paracoccidioidomicosis sera. The chemically deglycosylated extracellular released antigen, for 8 or 18 h showed 72 and 52% sensitivity with 98% and 92% specificity, respectively. Moreover, cross-reactivity with Paracoccidioides decreased to 4 and 16%, following deglycosylation for 8 or 18 h, respectively. The enzymatically treated antigen showed 52% of sensitivity, 92% of specificity and 8% cross-reactivity against Paracoccidioides. Deglycosylation of the H. capsulatum antigen improves its specificity and decreases its cross-reactivity against Paracoccidioides when using indirect ELISA for serodiagnosis. Therefore, it is recommended to deglycosylate the fungal extracellular released antigen for clinical serodiagnosis, and to monitor humoral immune responses during therapy of patients with the different clinical forms of histoplasmosis.

组织胞浆菌病的诊断取决于多种方法：直接临床检查，从临床样品培养物中分离真菌，组织病理学评估和血清学检测。在血清诊断分析中，荚膜组织胞浆H和M抗原糖蛋白已被广泛使用。然而，两种抗原均显示出局限性，这主要归因于它们与其他病原性真菌的糖蛋白的交叉反应，这损害了特异性，并产生假阳性，误诊和治疗失败。在这项工作中，我们从委内瑞拉7090 H.荚膜肿瘤中去糖基化的细胞外释放抗原临床分离株，使用化学和酶促方法，并通过间接酶联免疫吸附测定（ELISA）和组织胞浆菌病或PCM患者血清进行评估。在去糖基化之前，细胞外释放的抗原显示出62％的敏感性，66％的特异性和68％的与副球菌病的交叉反应性。化学去糖基化的细胞外释放抗原在8或18小时内分别显示出72％和52％的敏感性，以及98％和92％的特异性。此外，在去糖基化分别为8或18小时后，与副球菌的交叉反应性分别降低至4％和16％。经酶处理的抗原对副球菌显示52％的敏感性，92％的特异性和8％的交叉反应性。当使用间接ELISA进行血清诊断时，荚膜H.抗原的去糖基化可提高其特异性，并降低其对副球菌的交叉反应性。因此，建议对真菌胞外释放的抗原进行去糖基化以进行临床血清诊断，并在治疗具有不同临床形式组织胞浆菌病的患者期间监测体液免疫反应。