Decreased Production of Local Immunoglobulin A to<i>Pneumocystis carinii</i>in Bronchoalveolar Lavage Fluid from Human Immunodeficiency Virus-Positive Patients

Jalil, Abdul; Moja, Ph.; Lambert, Claude; Perol, M; Cotte, Laurent; Livrozet, Jean-Michel; Boibieux, A.; Vergnon, J.M.; Lucht, F.; Tran, Robert K.; Contini, Carlo; Genin, Christian

doi:10.1128/iai.68.3.1054-1060.2000

Cited by 11 publications

(6 citation statements)

References 36 publications

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“…These results support the concept of a role for IgA-mediated protection from Pneumocystis colonization and are consistent with clinical studies that showed mucosal antibodies to Pneumocystis are decreased in patients with PcP compared to HIV ϩ patients without PcP or with HIV-negative controls (27,31).…”

Section: Test) (D) Monkeys That Remained Pcsupporting

confidence: 79%

Relationship of Pneumocystis jiroveci Humoral Immunity to Prevention of Colonization and Chronic Obstructive Pulmonary Disease in a Primate Model of HIV Infection

Kling

Shipley²,

Patil³

et al. 2010

Infect Immun

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Pulmonary colonization by the opportunistic pathogen Pneumocystis jiroveci is common in HIV؉ subjects and has been associated with development of chronic obstructive pulmonary disease (COPD). Host and environmental factors associated with colonization susceptibility are undefined. Using a simian-human immunodeficiency virus (SHIV) model of HIV infection, the immunologic parameters associated with natural Pneumocystis jiroveci transmission were evaluated. SHIV-infected macaques were exposed to P. jiroveci by cohousing with immunosuppressed, P. jiroveci-colonized macaques in two independent experiments. Serial plasma and bronchoalveolar lavage (BAL) fluid samples were examined for changes in antibody titers to recombinant Pneumocystis-kexin protein (KEX1) and evidence of Pneumocystis colonization by nested PCR of BAL fluid. In experiment 1, 10 of 14 monkeys became Pneumocystis colonized (Pc ؉ ) by 8 weeks post-SHIV infection, while 4 animals remained Pneumocystis colonization negative (Pc ؊ ) throughout the study. In experiment 2, 11 of 17 animals became Pneumocystis colonized by 16 weeks post-SHIV infection, while 6 monkeys remained Pc ؊ . Baseline plasma KEX1-IgG titers were significantly higher in monkeys that remained Pc ؊ , compared to Pc ؉ monkeys, in experiments 1 (P ‫؍‬ 0.013) and 2 (P ‫؍‬ 0.022). Pc ؊ monkeys had greater percentages of Pneumocystis-specific memory B cells after SHIV infection compared to Pc ؉ monkeys (P ‫؍‬ 0.037). After SHIV infection, Pc ؉ monkeys developed progressive obstructive pulmonary disease, whereas Pc ؊ monkeys maintained normal lung function throughout the study. These results demonstrate a correlation between the KEX1 humoral response and the prevention of Pneumocystis colonization and obstructive lung disease in the SHIV model. In addition, these results indicate that an effective Pneumocystis-specific memory B-cell response is maintained despite progressive loss of CD4 ؉ T cells during SHIV infection.

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Section: Test) (D) Monkeys That Remained Pcsupporting

confidence: 79%

Relationship of Pneumocystis jiroveci Humoral Immunity to Prevention of Colonization and Chronic Obstructive Pulmonary Disease in a Primate Model of HIV Infection

Kling

Shipley²,

Patil³

et al. 2010

Infect Immun

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“…Those with current PCP experienced lower BALF antibody responses to Msg compared to those without a current diagnosis of PCP, similar to previously reported findings [ 30 ]. The mechanisms for lower IgA responses to Msg in HIV-infected patients with PCP are unclear.…”

Section: Discussionsupporting

confidence: 90%

“…jirovecii and what clinical and environmental factors drive these responses [3, 30, 31]. Tobacco smoking and ambient air pollution may influence PCP presentation and serum antibody responses to P .…”

Section: Introductionmentioning

confidence: 99%

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Effects of clinical and environmental factors on bronchoalveolar antibody responses to Pneumocystis jirovecii: A prospective cohort study of HIV+ patients

et al. 2017

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BackgroundHumoral immunity plays an important role against Pneumocystis jirovecii infection, yet clinical and environmental factors that impact bronchoalveolar antibody responses to P. jirovecii remain uncertain.MethodsFrom October 2008—December 2011 we enrolled consecutive HIV-infected adults admitted to San Francisco General Hospital (SFGH) who underwent bronchoscopy for suspected Pneumocystis pneumonia (PCP). We used local air quality monitoring data to assign ozone, nitrogen dioxide, and fine particulate matter exposures within 14 days prior to hospital admission. We quantified serum and bronchoalveolar lavage fluid (BALF) antibody responses to P. jirovecii major surface glycoprotein (Msg) recombinant constructs using ELISA. We then fit linear regression models to determine whether PCP and ambient air pollutants were associated with bronchoalveolar antibody responses to Msg.ResultsOf 81 HIV-infected patients enrolled, 47 (58%) were diagnosed with current PCP and 9 (11%) had a prior history of PCP. The median CD4+ count was 51 cells/μl (IQR 15–129) and 44% were current smokers. Serum antibody responses to Msg were statistically significantly predictive of BALF antibody responses, with the exception of IgG responses to MsgC8 and MsgC9. Prior PCP was associated with increased BALF IgA responses to Msg and current PCP was associated with decreased IgA responses. For instance, among patients without current PCP, those with prior PCP had a median 73.2 U (IQR 19.2–169) IgA response to MsgC1 compared to a 5.00 U (3.52–12.6) response among those without prior PCP. Additionally, current PCP predicted a 22.5 U (95%CI -39.2, -5.82) lower IgA response to MsgC1. Ambient ozone within the two weeks prior to hospital admission was associated with decreased BALF IgA responses to Msg while nitrogen dioxide was associated with increased IgA responses.ConclusionsPCP and ambient air pollutants were associated with BALF IgA responses to P. jirovecii in HIV-infected patients evaluated for suspected PCP.

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“…According to the majority of studies regarding PJP, both in HIV-positive and HIV-negative patients, an elevation in serum LDH concentration is a sign, although non-specific, that helps diagnostic confirmation and it is an important negative prognostic factor, since LDH elevation is a marker of cellular necrosis and an indicator of poor tissue perfusion. [42][43][44][45][46][47] Although literature has reported serum IgG deficit only as a predisposing factor for PJP in HIVpositive patients, [48][49][50][51][52] IgG role as opsonizing molecules and enhancer of macrophages respiratory burst (as already mentioned) may account for the worst observed prognosis in the group of patients with a lower mean serum IgG concentration. It is interesting to note that our patients mean serum procalcitonin concentration was 6.24±10.66 ng/mL, way too high to be related to a fungal infection in general and PJP in particular (PCT is usually below 2 ng/mL): this laboratory finding can be explained by some patients positivity to BAL microscopic examination, hemocultures and urinary antigens for Gram + and Grambacteria.…”

Section: Discussionmentioning

confidence: 99%

Pneumocystis pneumonia in HIV-negative immunocompromised patients in Internal Medicine ward

et al. 2020

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Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection typically observed in AIDS patients, for whom it represents a leading cause of death. However, its incidence among HIV-negative immunocompromised patients is progressively increasing, with a significantly higher mortality compared to that of AIDS-patients. We performed a retrospective observational study on HIV-negative patients with PJP. We aimed to determine their epidemiological features and their biohumoral and therapeutic variables, searching for a correlation between them and our patients’ outcome. We included all patients admitted to our Internal Medicine ward from January 2010 to June 2015, who were immunocompromised at the time of admission and had microbiologically confirmed PJP (association between compatible clinical-radiological findings and qualitative polymerase chain reaction positivity on bronchoalveolar lavage). Their immune impairment was assessed considering both their medical history and their complete white blood cells (WBC), differential WBC and their CD4 cell count. Transfer to Intensive Care Unit (ICU) or death was considered as an unfavorable clinical outcome, while hospital discharge or transfer to a non-ICU ward was considered as a favorable outcome. We included a total of 18 patients in our statistical analysis. We used Student’s t-test and Fischer’s χ-square test to compare, respectively, normally distributed continuous variables and non-continuous variables. Our patients’ mean age was 65±13.9 years. All of them had cancer, mostly hematological malignancies (13/18), notably non-Hodgkin lymphoma (NHL; 8/13). They were all being or had been recently treated with chemotherapy (10/18) and/or high-dose glucocorticoids, with full dose or during tapering (13/18). Statistical analysis of blood tests results showed a significant difference between mean serum lactate dehydrogenase (LDH) concentration in the group of patients with favorable vs unfavorable outcome. Also, mean serum immunoglobulins G (IgG) concentration and certain arterial blood gas findings (mean arterial paO2/FiO2, mean blood Ph and mean paCO2) at the time of admission were significantly different in the two groups of patients. 12/18 patient’s outcome turned out unfavorable. Trimethoprim + sulfamethoxazole (TMP+SMX) treatment was given to all our patients, with a mean duration of 13.39±9.36 days. Patients with a favorable outcome had received TMP+SMX treatment significantly earlier than those with an unfavorable outcome. Hematological malignancies, according to literature, confer the strongest predisposition to PJP. Both chemotherapy and high-dose Glucocorticoid treatment are well known predisposing factors. A remarkable elevation of serum LDH represents both a typical clinical feature and a well-known negative prognostic factor in PJP. Low IgG levels have never been reported as a negative prognostic factor, but their role in enhancing macrophage killing of pneumocystis may account for the worst observed prognosis in the group of patients with lower mean levels. Therefore, in order to reduce the heavy mortality rate associated with PJP, an early beginning of specific treatment is of utmost importance, and even if this is certainly true for many infectious diseases, the time gap is particularly limited in the setting of this type of pneumonia. Hence, PJP should be ruled out as soon as possible and, in case of a strong clinical- radiological suspicion, therapy should be started immediately, even while waiting for microbiological confirmation (especially in critically-ill patients).

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Decreased Production of Local Immunoglobulin A toPneumocystis cariniiin Bronchoalveolar Lavage Fluid from Human Immunodeficiency Virus-Positive Patients

Cited by 11 publications

References 36 publications

Relationship of Pneumocystis jiroveci Humoral Immunity to Prevention of Colonization and Chronic Obstructive Pulmonary Disease in a Primate Model of HIV Infection

Relationship of Pneumocystis jiroveci Humoral Immunity to Prevention of Colonization and Chronic Obstructive Pulmonary Disease in a Primate Model of HIV Infection

Effects of clinical and environmental factors on bronchoalveolar antibody responses to Pneumocystis jirovecii: A prospective cohort study of HIV+ patients

Pneumocystis pneumonia in HIV-negative immunocompromised patients in Internal Medicine ward

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