Evaluation of neutrophil CD 64 and CD 11b expression as early predictors of sepsis severity and outcome

CD64, the high affinity Fcy receptor 1, and CDllb, an alpha-subunit of the beta[2] integrin adhesion molecule, are specific neutrophil-surface antigens activated in response to systemic inflammation, therefore, they could potentially be used as early predictors of sepsis and the associated mortality in patients with systemic inflammatory response syndrome [SIRS]. Sixty-one SIRS patients with clinically suspected infection were enrolled and subjected to sepsis work-up, within the first 24 hours of sepsis onset, including complete blood count, blood culture, serum C-reactive protein [CRP] in addition to flow cytometric analysis of CD64 and GD11b. Patients were classified prospectively on the basis of clinical observation and blood culture results into two groups: SIRS with sepsis group [n=36] and SIRS without sepsis group [n=25] served as patient control. According to outcome, patients with sepsis were classified after a follow-up period up to 28 days after inclusion into two groups: survivors [n=29] and non-survivors [n=7]. A highly significant increase of neutrophil CD64 and CD11b expression was detected in the sepsis group as compared to the non-infected group. CD64 and CDllb expression had the best diagnostic performance for prediction of early-onset sepsis. Expression of CD64 at a cut-off value of 49% had 88.9% sensitivity, 92% specificity and 90.2% efficacy, while CD1 Ib expression at a cut-off value of 71% had 86.1% sensitivity, 84% specificity and 85.2% efficacy. Combined use of both markers yielded 91.7% sensitivity, 96% specificity and 93.4% efficacy. Sepsis survivors showed significantly lower expression of CD64 and CDllb as compared to non-survivors. An optimal cut-off value of 70% expression for CD64 predicted mortality with 100% sensitivity, 96.6% specificity and 97.2% efficacy. Meanwhile, a cut-off value of 86% for CDllb predicted mortality with 85.7% sensitivity, 93.1% specificity and 91.7% efficacy. Assessment of neutrophil CD64 and CDllb expression is superior to standard laboratory tests for early detection of sepsis, within the first 24 hours of sepsis onset, before the evolution of clinical signs which would facilitate therapeutic decisions. Prediction of outcome is an additional advantage borne by these two biomarkers

Immune-changes in sepsis

Sepsis is one of the most frequent complications in the surgical patient and one of the leading causes of mortality in intensive care units. Recent studies have shown that sepsis is a bimodal entity. The first phase is characterized by the systemic release of pro-inflammatory cytokines such as TNF-alpha, IL-1 and IL-8 and by activation of the complement and coagulation cascades. In the second phase, anti-inflammatory mediators such as TGF-beta, IL-10, Prostaglanding E[2] may be released in an effort to counteract ongoing inflammation. Depending whether pro or anti-inflammatory responses predominates, some people referred to a systemic inflammatory response syndrome [SIRS] and a compensatory anti-inflammatory response syndrome [CARS]. This work aimed to study selected immune markers [which represent both innate and adaptive immune systems] on the surface of white blood cells of critically ill patients who are expected to stay for a relatively long period in the ICU to identify a marker that can predict the development of nosocomial sepsis in the ICU [NICUS] patients while their stay in the ICU, a marker that can predict the development of mortality among ICU patients and a marker that can separate septic from non septic patients immediately alter admission to the ICU. Several markers which are expressed on the surface of different categories of white blood cells were measured CD 14 and HLA. DR for monocytes, CD16b CD11b and CD64 for PMNS and CD69, HLA. DR. CD57 and CD28 for lymphocytes. A total of 105 patients were admitted to the ICU department and differentiated into two groups 36 septic patients and 69 control [without sepsis]; with time observation of second group, 25 patients develop sepsis in the ICU [Nosco-mial ICU sepsis] consider as third group. A moderate prediction of noscomial sepsis can he expressed by CD 14 lower than 1602 molecule of CD64 pie cell of neutrophil is a good indicator of noscomial sepsis in critically ill patients. The absolute number of CD64 per cell of neutrophil [high than 1727 molecule/cell] identify septic patients on admission of ICU, while the positive lymphocytes higher than 31% can moderately identify septic patients early on ICU admission. The absolute number of CD64 on PMNs with a lower level than 2222 molecule/cell in first day of ICU admission showed a very good ability to predict 28[th] day mortality. Surface markers present on leukocytes could be used to diagnose early sepsis and predict hospital outcome. Measurement of mCD14 in patients in the ICU could be informative about the development of sepsis

Fc Gamma receptor IIa polymorphism in Egyptian patients with systemic lupus erythematosus

Systemic Lupus Erythematosus [SLE] is a complex, multifactorial auto-immune disease. Receptors for IgG play an important role in immune complex clearance. Several studies have identified polymorphisms of receptors for the Fc fragment of IgG [Fc Gamma R] as genetic factors influencing the susceptibility and course of such a disease. It has been also suggested that Fc Gamma RIIa polymorphism may be an important risk factor for development of lupus nephritis. This study was done to examine the frequency of Fc Gamma RIIa R/H131 polymorphism among Egyptian patients with SLE, as well as, to determine whether Fc Gamma RIIa polymorphism, represents a risk factor for both SLE susceptibility and lupus nephritis. Patients and Forty four Egyptian patients were diagnosed with SLE according to the American College of Rheumatology Criteria. Both SLE patients and healthy controls were genotyped for Fc Gamma RIIa R/H131 polymorphism using a single step allele PCR based method. No statistically significant difference was found in the frequency of FcyRlla genotypes [H/H, H/R and R/R] between SLE patients and normal controls [p > 0.05]. However, a small excess of R/R allele was seen in the SLE patients but this did not reach statistical significance [total SLE versus controls: OR 1.6, 95% CI 0.69-3.7, p > 0.05]. Moreover, a possible susceptibility to lupus nephritis which may be related to Fc Gamma RIIa R/R allele was suggested in the Egyptian patients, but this also did not reach statistical significance [OR 1.6, 95% Cl0.47-5.3, p > 0.05]. No statistically significant relation was found between Fc Gamma RIIa genotypes and age, age at onset and duration of the disease [p > 0.05]. Also, no statistically significant association between clinical manifestations and Fc Gamma RIIa polymorphism was demonstrated in this study. Serological assessments demonstrated that Fc Gamma RIIa H/H131 allele was significantly associated with double-stranded DNA antibody [OR < 1.95% CI0.27-3.3, p < 0.05], while no statistically significant association was demonstrated with anti-Smith antibody [p > 0.05]. Fc Gamma RIIa polymorphism may possibly constitute a minor determinant that could influence the susceptibility to SLE and lupus nephritis. However, it seems that it does not represent a well recognized genetic risk factor neither for SLE susceptibility nor for the development of lupus nephritis in Egyptian SLE patients