Kinetics of Anti‐Mannan Antibodies Useful in Confirming Invasive Candidiasis in Immunocompromised Patients

Deventer, A. J. M. Van; Goessens, W. H. F.; Zeijl, J.H. van; Mouton, Jan W.; Michel, M. F.; Verbrugh, Henri A.

doi:10.1111/j.1348-0421.1996.tb03327.x

Cited by 15 publications

(12 citation statements)

References 24 publications

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“…The sensitivities and specificities that we observed using individual proteins are within the ranges previously reported for antibody detection against a variety of antigens. Studies of IgG responses to ENO1 yielded sensitivities of 50 to 92% and specificities of 78 to 95% (14,15,16,26,33), and similar performances have been reported for tests against SAP (20,35), HWP1 (14), a 52-kDa metalloprotein (6), mannan (28,36), and CGTA (26). In attempts to overcome the diagnostic limitations of existing antibody tests, investigators have combined antibody responses against individual proteins with tests of antigen and/or metabolite detection.…”

Section: Discussionmentioning

confidence: 82%

“…There has been less enthusiasm for antibody detection as a diagnostic strategy because of concerns regarding false-negative tests in immunocompromised patients (26). Nevertheless, recent studies detecting antibodies against SAP (19,20), ENO1 (13,16), mannan (30,33,36), a 52-kDa metalloprotein (6), hyphal wall protein 1 (HWP1) (14), and a Candida albicans germ tube antigen (CGTA) (26) reported sensitivities and specificities that are consistent with those of other diagnostic markers, even among highly immunocompromised hosts like stem cell transplant and liver transplant recipients (11,12,21,31,34). Moreover, various combinations of an antibody test with an antigen test have been shown to be superior to either test alone in diagnosing systemic candidiasis (23,28,29).…”

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confidence: 99%

“…In the present project, we have chosen 12 proteins of diverse function and cellular localization to study as targets for antibody detection assays. These proteins are classified into four groups: classic cell wall proteins (Bgl2 and MUC1), glycolytic enzymes localized to the cell wall (ENO1, FBA1, GAP1, and PGK1), intracellular proteins localized to the cell wall (NOT5 and MET6), and intracellular proteins likely not localized to the cell wall (CAR1, RBT4, SET1, and IPF9162) (2,15,16,24,27,33). Our objectives were to determine if serum antibody responses against any purified recombinant antigens could reliably distinguish patients with systemic candidiasis from uninfected controls.…”

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confidence: 99%

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Immunoglobulin G Responses to a Panel of Candida albicans Antigens as Accurate and Early Markers for the Presence of Systemic Candidiasis

et al. 2008

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Despite shortcomings, cultures of blood and sterile sites remain the "gold standard" for diagnosing systemic candidiasis. Alternative diagnostic markers, including antibody detection, have been developed, but none are widely accepted. In this study, we used an enzyme-linked immunosorbent assay to measure serum antibody responses against 15 recombinant Candida albicans antigens among 60 patients with systemic candidiasis due to various Candida spp. and 24 uninfected controls. Mean immunoglobulin G (IgG) responses against all 15 antigens were significantly higher among patients with systemic candidiasis than among controls, whereas IgM responses were higher against only seven antigens. Using discriminant analysis that included IgG responses against the 15 antigens, we derived a mathematical prediction model that identified patients with systemic candidiasis with an error rate of 3.7%, a sensitivity of 96.6%, and a specificity of 95.6%. Furthermore, a prediction model using a subset of four antigens (SET1, ENO1, PGK1-2, and MUC1-2) identified through backward elimination and canonical correlation analyses performed as accurately as the full panel. Using the simplified model, we predicted systemic candidiasis in a separate test sample of 32 patients and controls with 100% sensitivity and 87.5% specificity. We also demonstrated that IgG titers against each of the four antigens included in the prediction model were significantly higher in convalescent-phase sera than in paired acutephase sera. Taken together, our findings suggest that IgG responses against a panel of candidal antigens might represent an accurate and early marker of systemic candidiasis, a hypothesis that should be tested in future trials.

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Section: Discussionmentioning

confidence: 82%

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confidence: 99%

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confidence: 99%

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Immunoglobulin G Responses to a Panel of Candida albicans Antigens as Accurate and Early Markers for the Presence of Systemic Candidiasis

et al. 2008

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“…3). It was shown recently that immunocompromised patients had increased antimannan antibody titers, which were observed shortly after the first clinical sign of invasive candidiasis (30). Further studies are needed to confirm that the determination of IgG1 anti-CW and IgG2 anti-PPM antibodies, in combination with ␤(1-3) glucan increases the specificity of diagnosis in immunocompromised patient groups.…”

Section: Discussionmentioning

confidence: 99%

Circulating β (1-3) Glucan and Immunoglobulin G Subclass Antibodies toCandida albicansCell Wall Antigens in Patients with Systemic Candidiasis

Kondori

Edebo

Mattsby‐Baltzer

2004

Clin Vaccine Immunol

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Invasive candidiasis in patients who are immunocompromised or in intensive care units (ICUs) presents both diagnostic and therapeutic problems. We previously described antibodies that were directed against Candida albicans cell wall fragments (CW), periodate-treated CW (CW IO4 ), phosphopeptidomannan (PPM), and ␤(1-3) glucan. In this study, circulating fungal antigens [mannan and ␤(1-3) glucan] and immunoglobulin G (IgG) subclass antibodies to these cell wall antigens (anti-CW) were analyzed in patients with systemic candidiasis. Sera were collected from 14 patients on two or three consecutive occasions, starting on the day when candidiasis was culture proven. The sera were analyzed by enzyme-linked immunosorbent assay. The control groups consisted of lactating mothers (n ‫؍‬ 9) (group I) who had breast milk that was positive for C. albicans and also had acute inflammation of the nipples, and age-matched blood donors (n ‫؍‬ 10) (group II). Within the first 3 weeks of Candida infection all of the patients were positive for ␤(1-3) glucan by the Gluspecy test, but no patients were positive for mannan in the less-sensitive Pastorex Candida test. The controls were negative for both ␤(1-3) glucan (<20 pg/ml) and mannan (<2.5 ng/ml). IgG1 anti-CW and IgG2 anti-PPM antibodies were the most discriminatory antibodies. The ratio of IgG1 anti-CW to IgG2 anti-PPM was significantly lower in nonsurviving patients than in the other patients within the first week of candidiasis (P ‫؍‬ 0.019). The IgG2 levels of anti-CW IO4 and antiglucan antibodies correlated strongly (r ‫؍‬ 0.681; P < 0.0001), and the absence of these antibodies was associated with increased levels of ␤(1-3) glucan. Increased levels of IgG1 anti-CW or IgG2 anti-PPM antibodies (titer of >3 logs) or of a combination of the two antibodies (log sum, >5) showed 92% sensitivity, 100% specificity, and positive predictive values. In conclusion, ␤(1-3) glucan and the two subclass antibodies appear to be early specific markers for the laboratory diagnosis of candidiasis. Furthermore, the kinetics of ␤(1-3) glucan appearance in serum may assist in evaluating the therapeutic efficacy of antifungal treatments.

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“…Following the observation that an antibody response developed as candida colonisation in hospitalised patients increased [31,52], confidence in the specificity of these tests decreased. Despite several studies demonstrating the usefulness of anti-Candida antibody detection tests for diagnosis [53,54], these tests are seldom requested by physicians in clinical practice. The reason given is the absence of clear-cut discrimination between infected and colonised patients.…”

Section: Discussionmentioning

confidence: 99%

Combined detection of mannanaemia and anti-mannan antibodies as a strategy for the diagnosis of systemic infection caused by pathogenic Candida species

Sendid

Poirot

Tabouret

et al. 2002

Journal of Medical Microbiology

142

116

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Kinetics of Anti‐Mannan Antibodies Useful in Confirming Invasive Candidiasis in Immunocompromised Patients

Cited by 15 publications

References 24 publications

Immunoglobulin G Responses to a Panel of Candida albicans Antigens as Accurate and Early Markers for the Presence of Systemic Candidiasis

Immunoglobulin G Responses to a Panel of Candida albicans Antigens as Accurate and Early Markers for the Presence of Systemic Candidiasis

Circulating β (1-3) Glucan and Immunoglobulin G Subclass Antibodies toCandida albicansCell Wall Antigens in Patients with Systemic Candidiasis

Combined detection of mannanaemia and anti-mannan antibodies as a strategy for the diagnosis of systemic infection caused by pathogenic Candida species

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