Detection of IgM and IgG antibodies to <i>Cryptococcus neoformans</i> proteins in blood donors and HIV patients with active cryptococcosis

Chai, Hwa Chia; Tay, Sun Tee

doi:10.1111/j.1439-0507.2008.01549.x

Cited by 8 publications

(6 citation statements)

References 20 publications

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“…Remarkably, anti-cryptococcal IgM and IgG antibodies were detected in considerably high frequencies even in sera from healthy human individuals, which we categorize as "preexisting" antibodies. This finding is in accordance with previously published results, demonstrating the presence of antibodies directed against cryptococcal CPS (33,(47)(48)(49)(50)(51)(52)(53)(54)56), cryptococcal proteins (58)(59)(60)(61)(62) or mannoproteins (57) in human sera, independent of cryptococcal disease or the HIV status.…”

Section: Discussionsupporting

confidence: 93%

“…Similarly, previous studies showed increased anti-glucuronoxylomannan (GXM) titers in HIV-negative CM patients compared to healthy individuals (19) or HIV-positive cryptococcosis patients (61). However, in our study similar titers of anti-cryptococcal IgG antibody were detected in HIV-positive CM patients and healthy individuals, confirming previous reports (55,58,62). We hypothesize, that severely immunosuppressed AIDS patients (CD4 + T cell count <250 cells/µL) are not able to mount a…”

Section: Discussionsupporting

confidence: 91%

“…Various studies demonstrated the ubiquitous presence of antibodies in human sera directed against cryptococcal capsular polysaccharides (47-56), mannoproteins (57), and cryptococcal proteins (58)(59)(60)(61)(62), regardless of predisposing HIV infection or even previous history of cryptococcal disease. However, the C. neoformans proteins targeted by these human antibodies have not been identified so far.…”

Section: Introductionmentioning

confidence: 99%

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Identification of Disease-Associated Cryptococcal Proteins Reactive With Serum IgG From Cryptococcal Meningitis Patients

et al. 2021

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Cryptococcus neoformans, an opportunistic fungal pathogen ubiquitously present in the environment, causes cryptococcal meningitis (CM) mainly in immunocompromised patients, such as AIDS patients. We aimed to identify disease-associated cryptococcal protein antigens targeted by the human humoral immune response. Therefore, we used sera from Colombian CM patients, with or without HIV infection, and from healthy individuals living in the same region. Serological analysis revealed increased titers of anti-cryptococcal IgG in HIV-negative CM patients, but not HIV-positive CM patients, compared to healthy controls. In contrast, titers of anti-cryptococcal IgM were not affected by CM. Furthermore, we detected pre-existing IgG and IgM antibodies even in sera from healthy individuals. The observed induction of anti-cryptococcal IgG but not IgM during CM was supported by analysis of sera from C. neoformans-infected mice. Stronger increase in IgG was found in wild type mice with high lung fungal burden compared to IL-4Rα-deficient mice showing low lung fungal burden. To identify the proteins targeted by human anti-cryptococcal IgG antibodies, we applied a quantitative 2D immunoproteome approach identifying cryptococcal protein spots preferentially recognized by sera from CM patients or healthy individuals followed by mass spectrometry analysis. Twenty-three cryptococcal proteins were recombinantly expressed and confirmed to be immunoreactive with human sera. Fourteen of them were newly described as immunoreactive proteins. Twelve proteins were classified as disease-associated antigens, based on significantly stronger immunoreactivity with sera from CM patients compared to healthy individuals. The proteins identified in our screen significantly expand the pool of cryptococcal proteins with potential for (i) development of novel anti-cryptococcal agents based on implications in cryptococcal virulence or survival, or (ii) development of an anti-cryptococcal vaccine, as several candidates lack homology to human proteins and are localized extracellularly. Furthermore, this study defines pre-existing anti-cryptococcal immunoreactivity in healthy individuals at a molecular level, identifying target antigens recognized by sera from healthy control persons.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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Identification of Disease-Associated Cryptococcal Proteins Reactive With Serum IgG From Cryptococcal Meningitis Patients

et al. 2021

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“…Protein was extracted from each cryptococcal strain using a method described previously (53). Briefly, 10 ml of a mid-log-phase culture was pelleted, washed twice in cold water, and snap-frozen in liquid nitrogen.…”

Section: Methodsmentioning

confidence: 99%

Factors Required for Activation of Urease as a Virulence Determinant in Cryptococcus neoformans

Singh

Panting

Varma

et al. 2013

mBio

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Urease in Cryptococcus neoformans plays an important role in fungal dissemination to the brain and causing meningoencephalitis. Although urea is not required for synthesis of apourease encoded by URE1, the available nitrogen source affected the expression of URE1 as well as the level of the enzyme activity. Activation of the apoenzyme requires three accessory proteins, Ure4, Ure6, and Ure7, which are homologs of the bacterial urease accessory proteins UreD, UreF, and UreG, respectively. A yeast two-hybrid assay showed positive interaction of Ure1 with the three accessory proteins encoded by URE4, URE6, and URE7. Metalloproteomic analysis of cryptococcal lysates using inductively coupled plasma mass spectrometry (ICP-MS) and a biochemical assay of urease activity showed that, as in many other organisms, urease is a metallocentric enzyme that requires nickel transported by Nic1 for its catalytic activity. The Ure7 accessory protein (bacterial UreG homolog) binds nickel likely via its conserved histidine-rich domain and appears to be responsible for the incorporation of Ni2+ into the apourease. Although the cryptococcal genome lacks the bacterial UreE homolog, Ure7 appears to combine the functions of bacterial UreE and UreG, thus making this pathogen more similar to that seen with the plant system. Brain invasion by the ure1, ure7, and nic1 mutant strains that lack urease activity was significantly less effective in a mouse model. This indicated that an activated urease and not the Ure1 protein was responsible for enhancement of brain invasion and that the factors required for urease activation in C. neoformans resemble those of plants more than those of bacteria.

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“…While cases of cryptococcosis are most often encountered as acute infection, most are caused by reactivation of latent infection. Evidence for this stems from high prevalence of cryptococcal antibodies in healthy individuals 40,41 and the ability of cryptococci to infect macrophages and remain latent. 42 Factors that trigger reactivation of infection are unknown.…”

Section: Virulence Pathogenesis and Latencymentioning

confidence: 99%

Pulmonary Cryptococcosis

Chang

Sorrell

Chen

2015

Semin Respir Crit Care Med

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Inhalation of Cryptococcus into the respiratory system is the main route of acquisition of human infection, yet pulmonary cryptococcosis goes mostly unrecognized by many clinicians. This delay in diagnosis, or misdiagnosis, of lung infections is due in part to frequently subtle clinical manifestations such as a subacute or chronic cough, a broad differential of diagnostic possibilities for associated pulmonary masses (cryptococcomas) and, on occasion, negative respiratory tract cultures. Hematogenous dissemination from the lung can result in protean manifestations, the most severe of which is meningoencephalitis. There are few clinical studies of pulmonary cryptococcosis and its pathogenesis is poorly understood. The main purpose of this review is to describe the epidemiology, clinical presentation, diagnosis, and treatment of pulmonary cryptococcosis to increase clinician's awareness of this diagnostic possibility and to enhance clinical management. Useful pointers to the approach and management of pulmonary cryptococcosis and the implications of disseminated disease are included, together with recommendations for future research.

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Detection of IgM and IgG antibodies to Cryptococcus neoformans proteins in blood donors and HIV patients with active cryptococcosis

Cited by 8 publications

References 20 publications

Identification of Disease-Associated Cryptococcal Proteins Reactive With Serum IgG From Cryptococcal Meningitis Patients

Identification of Disease-Associated Cryptococcal Proteins Reactive With Serum IgG From Cryptococcal Meningitis Patients

Factors Required for Activation of Urease as a Virulence Determinant in Cryptococcus neoformans

Pulmonary Cryptococcosis

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