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Immunocompetence, immunosuppression, and human breast cancer. III. Prognostic significance of initial level of immunocompetence in early and advanced disease.

The prognostic significance of immunocompetence determined at diagnosis was analyzed in 158 operable breast cancer patients followed for 3--6 years, in terms of disease recurrence and of length of disease-free period (DFP) and in 52 patients with metastatic disease in terms of length of survival. In vitro lymphocyte stimulation by PPD and PHA were of higher predictive value with respect to probability of disease recurrence than in vivo cutaneous reactivity to PPD and DNCB. Conversely, length of DFP and of survival were found to correlate better with in vivo than within vitro parameters. Absolute number of peripheral blood lymphocytes (PBL) and percent of E-rosette-forming cells (E-RFC) proved devoid of prognostic value. Prognostic separation was best brought out upon analysis by integrated score of immunocompetence, comprising the four functional parameters. Probability of disease recurrence was 0.43 for all operable patients, as calculated by actuarial method 48 months postoperatively; it was 0.26 for optimal and 0.61 for suboptimal responders (P less than 0.0001). Separate analysis of Stage 1 (N0) and Stage II (N+) patients revealed prognostic segregation within each stage: probability of recurrence in Stage I was 0.06 for optimal vs. 0.41 for suboptimal responders (P less than 0.001) and in Stage II it was 0.45 vs. 0.79, respectively (P less than 0.01). These findings may prove valuable for a more selective patient allocation for post-mastectomy adjuvant therapy. Length of DFP was found inversely proportional to initial immunocompetence, with a mean of 23.5 months for good responders and 12.8 months for poor responders (P less than 0.01). Length of survival of metastatic patients was found to correlate with initial (pretreatment) levels of immunocompetence, mean survival being 29.5 months for those with preserved immune function and 12.3 months for the immunosuppressed (P less than 0.001). It was concluded that initial immunocompetence, determined by parameters of cell-mediated immunity, shows strong prognostic association with the subsequently observed course of human breast cancer.

Adult↗

Immunocompetent for immunotherapy? A study of the immunocompetence of cervical cancer patients.

Sixty-five patients with cervical carcinoma and 17 control subjects were studied to determine immunocompetence as a prerequisite for immunotherapy using live virus vectors. T-cell immunity, measured by surface phenotype and proliferative assays, was reduced with increasing volume of invasive disease, and independent of treatment effects. Both the CD4+ and CD8+ subsets were affected so that the CD4:8 ratio remained within normal limits. In contrast B-cell number, immunoglobulins and complement were normal as were in vivo responses to a polysaccharide vaccine. Thus, determination of immunocompetence prior to use of live vector immunotherapy requires assessment of each individual subject, especially in those with advanced disease.

Journal Article↗

Severe thrombocytopenia after cytomegalovirus infection in an immunocompetent host--correlation between CMV infection and platelet count in immunocompetent host.

We report a case of severe thrombocytopenia after cytomegalovirus mononucleosis and the changes of the platelet count in 13 cases (including documented case) with CMV mononucleosis (4 cases) or Epstein-Barr virus mononucleosis (9 cases), who were admitted to our hospital from 1991 to 1995. A decrease of the platelet count was observed in some patients at diagnosis compared to the following days, suggesting that thrombocytopenia may be induced by CMV as well as EBV, and mild thrombocytopenia may be more frequent than expected after CMV infection in immunocompetent adults, although severe thrombocytopenia is rare.

Adult↗

[In vitro parameters for the comprehension of the immunocompetence of chickens of different lines. 2. Testing an immunocompetent parameter as a selection criterion in the chicken].

A cytotoxicity test using blood and saccharomyces cells (SCT) was experimentally applied in a sample of pedigreed commercial chickens from different lines over 3 generations to test its usefulness as a parameter for the nonspecific defense capacity. The results clearly show a significant difference between the SC rates in the different lines. Positive heritabilities exist between the SC rates of the 3 generations. The correlations between SC rates of males in the first generation and parameters of layer productivity of their daughters are nonsignificant. The possibility to integrate the parameter SC into the selection index is critically discussed.

Animals↗

The immunocompetence handicap hypothesis: testing the genetic predictions

The immunocompetence handicap hypothesis suggests that the immune system competes for resources with sexually selected ornaments; variation in ornaments might reflect genetic variation for immunocompetence. We tested this genetic prediction by mating scorpionfly females to males differing in the expression of a condition-dependent ornament trait, saliva secretion, and then comparing offspring immunocompetence. We found several indications of an immunocompetence handicap in our study: females had superior immunocompetence compared with males, the different immune traits were positively correlated, and there were indications of genetic variation in immune traits. However, we found no significant difference in the immunocompetence of offspring derived from males differing in ornament expression, only a tendency for sons of ornamented males to possess slightly better immunocompetence. The estimated effect of fathers on offspring immunocompetence was rather small, but it might be a sufficient benefit of female choice, provided that the costs of choice are small. We conclude that the genetic benefit of female choice is small concerning offspring immunocompetence, but the immunocompetence handicap principle might nevertheless work in scorpionflies.

Journal Article↗

Oral infection with Porphyromonas gingivalis and induced alveolar bone loss in immunocompetent and severe combined immunodeficient mice.

The suitability of a mouse model for host response in the induction of alveolar bone loss by Porphyromonas gingivalis was explored. The mouths of immunocompetent and severe combined immunodeficient (SCID) mice were infected with P. gingivalis ATCC 53977. P. gingivalis was not isolated from the mouths of these mice before infection, but was present at least 42 days after infection. P. gingivalis-specific IgG was present in sera from the infected, immunocompetent mice at the end of these experiments (42 days). Specific IgG was not present in sham-infected or uninfected immunocompetent mice, nor in any immunodeficient mice. Specific IgM was not present in any sera at 42 days. Infected, immunocompetent mice of two strains showed significant bone loss in comparison to sham-infected or uninfected immunocompetent mice (p < 0.05). Infected SCID mice, which are genetically lacking both B and T lymphocytes, also showed significant bone loss compared with sham-infected or uninfected SCID mice (p < 0.05). However, the degree of bone loss was greater in immunocompetent than immunodeficient mice: the relative amount of bone in infected mice was 77% of that in sham-infected immunocompetent mice, and 86% of sham values in SCID mice (p = 0.025). Thus oral infection of mice is a feasible model for studying the effects of host response on P. gingivalis-induced alveolar bone loss. Because bone loss was induced both in immunocompetent and SCID mice but was greater in immunocompetent mice, it appears that neither B nor T cells are absolutely necessary for bone resorption in response to P. gingivalis infection but they may significantly modulate the degree of resorption.

Alveolar Bone Loss↗

Does clutch size evolve in response to parasites and immunocompetence?

Parasites have been argued to influence clutch size evolution, but past work and theory has largely focused on within-species optimization solutions rather than clearly addressing among-species variation. The effects of parasites on clutch size variation among species can be complex, however, because different parasites can induce age-specific differences in mortality that can cause clutch size to evolve in different directions. We provide a conceptual argument that differences in immunocompetence among species should integrate differences in overall levels of parasite-induced mortality to which a species is exposed. We test this assumption and show that mortality caused by parasites is positively correlated with immunocompetence measured by cell-mediated measures. Under life history theory, clutch size should increase with increased adult mortality and decrease with increased juvenile mortality. Using immunocompetence as a general assay of parasite-induced mortality, we tested these predictions by using data for 25 species. We found that clutch size increased strongly with adult immunocompetence. In contrast, clutch size decreased weakly with increased juvenile immunocompetence. But, immunocompetence of juveniles may be constrained by selection on adults, and, when we controlled for adult immunocompetence, clutch size decreased with juvenile immunocompetence. Thus, immunocompetence seems to reflect evolutionary differences in parasite virulence experienced by species, and differences in age-specific parasite virulence appears to exert opposite selection on clutch size evolution.

Animals↗

Cryptococcosis in apparently immunocompetent patients.

BACKGROUND: Few reports have described the clinical and microbiological features of cryptococcosis in immunocompetent patients. AIM: To compare clinical presentations and outcomes of cryptococcosis in immunocompetent vs. immunocompromised patients. DESIGN: Retrospective case series. METHODS: All culture- or histology-confirmed cases (n = 46) of cryptococcosis in two acute hospitals in Hong Kong (1995-2005) were included. Clinical presentations, rates of fungaemia, cerebrospinal fluid (CSF) parameters and clinical outcomes were recorded. RESULTS: Twenty patients (43.5%) were apparently immunocompetent, 17 (37.0%) had predisposing factors other than HIV infection, and 9 (19.6%) were HIV-positive. Thirty-one (67.4%) presented with meningitis, four (8.7%) with pulmonary cryptococcosis, and 11 (23.9%) with extraneural, extrapulmonary cryptococcosis. Of the immunocompetent patients with retrievable isolates (n = 8), three (37.5%) were Cryptococcus gattii; all isolates (n = 6) from immunocompromised patients were Cryptococcus neoformans var. grubii. Immunocompetent patients more commonly presented with meningitis (80.0% vs. 47.1%, p = 0.03), and tended toward lower rates of fungaemia (10.0% vs. 35.3%, p = 0.06) and mortality (25.0% vs. 52.9%, p = 0.06). Death was associated with fungaemia (p = 0.01) and underlying malignancy (p < 0.01). In cryptococcal meningitis, immunocompetent patients had longer mean time from illness onset to presentation (34.4 vs. 12.6 days, p = 0.02), more intense inflammatory responses (CSF: white blood cells 108 vs. 35 x 10(9)/l, p = 0.03; protein 1.61 g/l vs. 0.79 g/l, p = 0.07), less fungaemia (0% vs. 26.7%, p = 0.04) and more satisfactory clinical outcomes (81.3% vs. 46.7%, p = 0.04). DISCUSSION: A substantial proportion of patients with cryptococcosis are apparently immunocompetent. C. neoformans var. grubii and C. gattii are the common causes. Immunocompetent patients tend to present with localized, indolent neurological disease, with more intense inflammatory responses but better clinical outcomes.

Adult↗

[Animal immunocompetence and its effect on population regulation and life history trade-off].

Immunocompetence is a common conception in biomedical and animal sciences, and refers to the ability of organisms against diseases. In recent years, a new field, ecological immunology, has been received much attention, which deals with the variation of immunocompetence in wildlife by immune methods. This paper introduced the conception of immunocompetence, the factors affecting its performance, and its roles in regulating animal population dynamics. Some hypotheses on population regulation in small mammals, such as immunocompetence handicap hypothesis, immunocompetence selection hypothesis and winter immune enhancement hypothesis were summarized. The relationships among energy metabolism, endocrine controlling mechanism and immune system were introduced, and the recent progress on immunocompetence and life history trade-off was analyzed. The trade-off between survival and immunocompetence, as well as between reproduction and immunocompetence were discussed, and some developing perspectives and new problems in ecological immunology were proposed.

Animals↗

Contribution of immunocompetence to the antibacterial activities of ciprofloxacin and moxifloxacin in an in vitro pharmacodynamic model.

Traditional in vitro models used to simulate human pharmacokinetics and to characterize the pharmacodynamics of antibacterial agents represent a totally immunosuppressed condition. However, host defense mechanisms contribute to the elimination of the pathogen from the infectious site in most of the patients suffering from infectious diseases. Therefore, the attempt was made to introduce immunocompetence into an in vitro pharmacodynamic model. Immunocompetence was added either by using J774 macrophages growing as adherent monolayers in cell culture flasks, or by using a newly developed ex vivo model. This ex vivo model consists of sponges which have been implanted into rats for 24 h. After 24 h the sponges are explanted; at this point in time the sponges are soaked with an inflammatory exudate to which the bacteria to be tested are added. Into a slightly modified one-compartment model according to Grasso the explanted sponges which are entrapped in dialysis tubings are added. Neither the bacteria nor the inflammatory proteins nor the immunocompetent cells escape from the explants. Thus, it is possible to simulate antibiotic kinetics without diluting bacteria, the polymorphonuclear cells (PMN) or the inflammatory exudates. This ex vivo model and the J774 cell culture model were used to compare the antibacterial effects of ciprofloxacin against Pseudomonas aeruginosa and moxifloxacin against Streptococcus pneumoniae either in the absence or presence of any immunocompetence. In general, the presence of J774 macrophages resulted in an increased reduction of viable counts by 1 log10 titer. However, an increased killing of the bacteria studied by 3 to 4 log10 titers was seen in the presence of PMN and an inflammatory exudate. This increase in bacterial clearance is very well in agreement with the data obtained in animal models of infection in immunocompetent animals as compared to immunocompromised animals. Thus, it is possible to introduce immunocompetence into an in vitro model in order to simulate pharmacokinetics of antibacterial agents in the presence of an inflammatory exudate and immunocompetent cells. The use of this more complex model may complement the well-established in vitro kinetic simulation models.

Animals↗

TP53 polymorphism of exon 4 at codon 72 in cutaneous squamous cell carcinoma and benign epithelial lesions of renal transplant recipients and immunocompetent individuals: lack of correlation with human papillomavirus status.

A common polymorphism at codon 72 of exon 4 encoding either arginine or proline has been shown to confer a susceptibility to the development of skin tumor in renal transplant recipients. Moreover, this polymorphism may affect proteolytic degradation of p53 promoted by E6 protein from mucosal human papillomaviruses and represent a risk factor for human-papillomavirus-induced carcinogenesis. In this study, we analyzed the human papillomavirus presence and the TP53 allele distribution in cutaneous squamous cell carcinoma of renal transplant recipients and immunocompetent patients. Fifty-three squamous cell carcinomas from 40 renal transplant recipients, 50 benign epithelial skin lesions from 50 renal transplant recipients with no history of skin cancer, 51 squamous cell carcinomas from immunocompetent patients, and 29 blood samples from immunocompetent individuals without skin cancer were investigated. Human papillomavirus DNA was detected using polymerase chain reaction performed with two pairs of primers (MY09-MY11 and FAP59-FAP64). TP53 allele distribution was studied by denaturing gradient gel electrophoresis assay, followed by sequencing analysis. Human papillomavirus DNA was detected in 64% of squamous cell carcinoma and 79% of benign epithelial lesions from renal transplant recipients (NS) and only in 37% of squamous cell carcinoma from immunocompetent patients (p < 0.05). Mucosal oncogenic human papillomavirus types were predominant in squamous cell carcinoma from both renal transplant recipients and immunocompetent patients. Rate of arginine homozygosity in squamous cell carcinoma from renal transplant recipients was significantly higher (83%) than in immunocompetent patients with or without squamous cell carcinoma (60% and 59%, respectively). Our results suggest that TP53 arginine/arginine genotype could represent a potential risk factor for the development of squamous cell carcinoma in renal transplant recipients compared to immunocompetent patients. No association between TP53 arginine/arginine genotype and human papillomavirus status could be determined, however.

Carcinoma, Squamous Cell↗

Rhodococcus equi infections in immunocompetent hosts: case report and review.

Rhodococcus equi is an unusual cause of infection in humans. Infection in immunocompetent patients is extremely rare-only 19 cases in immunocompetent hosts have been reported. Localized infections represent nearly 50% of reported cases. Pulmonary infections account for only 42% of infections in immunocompetent hosts, compared with 84% of infections in immunocompromised hosts. The mortality rate among immunocompetent patients is approximately 11%, compared with rates of 50%-55% among human immunodeficiency virus (HIV)-infected patients and 20%-25% among non-HIV-infected immunocompromised patients. Treatment of infections in immunocompetent hosts depends on the site of infection. Serious infections need to be treated with combinations of parenteral antibiotics, followed by combinations of oral antibiotics. Surgical treatment is necessary for certain types of local infections. We report a pulmonary infection due to R. equi in an immunocompetent patient, and we review all reported cases of R. equi infection in immunocompetent hosts.

Actinomycetales Infections↗

Pulmonary cryptococcosis: comparison of clinical and radiographic characteristics in immunocompetent and immunocompromised patients.

STUDY OBJECTIVES: We compared the clinical characteristics and imaging findings between immunocompetent and immunocompromised patients in whom pulmonary cryptococcosis had been diagnosed to define the role of serum cryptococcal antigen (sCRAG) and radiographs during a follow-up period of up to 1 year. DESIGN: Retrospective cohort study. SETTING: University hospital. PATIENTS: The clinical records, chest radiographs, and CT scan findings of 13 immunocompetent and 16 immunocompromised patients with a diagnosis based on cerebrospinal fluid (CSF) culture, sCRAG titers, and cytologic or histologic confirmation of the presence of pulmonary cryptococcosis were reviewed during the course of the study. Two thoracic radiologists reviewed chest radiographs and CT scans for morphologic characteristics and the distribution of parenchymal abnormalities, and a final reading was reached by consensus. The correlation between serial radiographs and sCRAG titers was examined in 9 immunocompetent and 10 immunocompromised patients. MEASUREMENTS: Serum or CSF cryptococcal antigen. RESULTS: The most common clinical symptom was cough, which was present in 24 patients (82.8%). Pulmonary nodules were the most frequent radiologic abnormality. Cavitation within nodules and parenchymal consolidation were significantly less common in immunocompetent patients compared to immunocompromised patients (p = 0.02 and p = 0.05, respectively). Immunocompromised patients tended to have a larger extent of pulmonary involvement than immunocompetent patients, the changes seen on their serial radiographs were more variable, and their corresponding sCRAG titers were higher (> 1:256). In the immunocompetent patients, the radiographic characteristics of lesions usually improved with a corresponding decrease in sCRAG titers over time. CONCLUSIONS: Our study suggests that pulmonary cryptococcosis usually follows a benign clinical course in immunocompetent patients. Immunocompromised patients often undergo an evolution to cavitary lesions that represent a more aggressive disease nature. Serial radiographic changes and changes in sCRAG titers reliably reflect disease progression and the response to therapy.

Adolescent↗

Surgery for lung abscess in immunocompetent and immunocompromised children.

PURPOSE: The aim of this study was to evaluate the surgical management results of lung abscess in immunocompetent and immunocompromised children. METHODS: Surgery was performed on 30 children with lung abscess or necrotizing pneumonia refractory to medical treatment in a 12-year period. Of them, 23 were immunocompetent, and 7 were immunocompromised. Pulmonary resection was performed including unilateral lung in 28, bilateral in 2, and 2 lobes in 6. Concomitant decortication was performed in 18 (78.2%) immunocompetent patients. RESULTS: Increased incidence of surgery for lung abscess was caused mainly by drug-resistant and fungal infection. Surgery was performed commonly for bacterial lung abscess on patients less than 5 years old and fungal lung abscess on adolescence. A multiple small abscess was the predominant type of abscess in immunocompetent patients, whereas 2-lobe involvement tended to occur in immunocompromised patients. Fungal lung abscess tended to occur on left lung and in female patients. Left lower lobe was involved most commonly in both groups of patients in which majority need lobectomy. Immunocompromised patients required a more extensive pulmonary resection. There were 3 postoperative complications (morbidity of 10.2%) with no postoperative mortality. Length of postoperative hospital stay ranged from 6 to 85 days with average of 18.4 days. CONCLUSIONS: The incidence and pattern of lung abscess that required surgery between immunocompetent and immunocompromised children were different. A more aggressive, extensive surgical procedure is preferable for immunocompromised patients, and the surgical results were comparatively excellent to immunocompetent patients. However, the prognosis of immunocompromised children depends on their underlying disease process.

Adolescent↗

Survival in Hodgkin's disease: the role of immunocompetence and other major risk factors.

The prognostic value of age, sex, symptoms, histopathology, lymphocyte count, skin tests, immunocompetence (lymphocyte response profile to a spectrum of PHA concentrations), and stage was evaluated in 35 previously untreated patients with Hodgkin's disease by multiple linear regression and logistic analysis. Immunocompetence exhibited the highest correlation (R = 0.537) with survival status and was required as a common denominator for deriving best sets of two or more variables. In addition, immunocompetence contributed to all other variables combined (p = 0.023), whereas stage did not (p = 0.116). Immunocompetence, age, symptoms, and histopathology generated a highly discriminant (R = 0.784) model not improved by stage or by other variables (p greater than or equal to 0.159). The utility and generalizability of this model are shown by a correct classification of 91.2% of cases according to expected versus actual survival status and by a predicted correlation (R) of 0.71, respectively, neither improved by sex, lymphocyte count, skin tests, or stage. In comparison, the conventional triad of stage, symptoms, and histopathology correctly classified only 70.6% of cases and showed actual and predicted correlations with survival status of R = 0.550 and R = 0.51. We conclude that immunocompetence is a powerful discriminant risk factor in Hodgkin's disease that exerts a pivotal role on survival and serves as a basis for models of greater discriminant power and generalizability than the conventional stage-based evaluation triad. Immunocompetence-based models are expected to provide a more discriminating basis for clinical evaluation, prediction of prognosis, and treatment selection for patients with Hodgkin's disease.

Adult↗