The evaluation of some serum immunochemical markers in early onset pre-eclamptic women from Algeria.

PROBLEM: Progress in understanding the underlying mechanism responsible for the syndrome pre-eclampsia should reconfigure antenatal clinical care and minimize human and financial costs, yet at present there is no accurate theory that permits development of reliable predictive tests and prophylactic intervention to mitigate disease. To contribute to this ongoing effort, we aimed to assess various circulating markers pertaining to different theories. METHOD OF STUDY: Serum samples from thirty-four women with established early onset preeclampsia (ePE) were assessed in terms of oxidative stress (malondialdehyde- MDA), angiogenic status (PlGF & sFLT-1), complement system (The alternative pathway- AP50 and complement factor H- CFH) and circulating inflammatory markers (Interleukin 6- IL-6 & Procalcitonin- PCT). Control groups of gestational age matched patients included 20 gestational hypertensive (GH) and six normotensive pregnant women (NPW). RESULTS: Our work shows that PlGF is the only serum marker who does exhibit a continued decrease from NPW to GH to ePE (rpearson = -.428, p = .002). The ePE group had a profound impairment in circulating PlGF (66.93 ± 20.62 pg/ml) compared to GH (142.67 ± 39.79 pg/ml; p = .069) and NPW (636.83 ± 392.66 pg/ml; p = .002). Then, PlGF >71.29 pg/ml pg/ml is the cut-off that has the highest negative predictive value enabling exclusion of ePE (Sp 78%, Se 70%, p = .000). No such interesting results could be obtained with the other markers. CONCLUSION: Our data confirm that the angiogenic factor PlGF may be highly relevant in biological mechanisms underlying the development of ePE.

NLR: A Cost-effective Nomogram to Guide Therapeutic Interventions in COVID-19.

COVID-19 exhibits a non-yet elucidated heterogeneity dominated by mild form of the illness. Nevertheless, mortality is frequent among patients with a delayed innate immune response that suddenly exacerbates during the second week after admission leading to a lethal over inflammation. Therefore, this rapid and unpredictable deterioration requires timely prediction of COVID-19 refractoriness and critical illness. The two biomarkers readily available in routine laboratories, blood lymphocytes and neutrophil counts, are expected to provide an accurate clinical tool to incline reasonable medication and care because lymphopenia marks immune exhaustion while neutrophilia demonstrates the immunological exuberation. Meanwhile, combining the two parameters as a Neutrophil-to-lymphocyte ratio (NLR) helps to constitute a powerful predictive and prognostic nomogram. This scoring tool allows clinicians to stratify COVID-19 severities on admission and guide early interventions to accelerate recovery and shorten the course of disease in order to alleviate the shortage of medical resources and reduce mortality.

Semi-solid phase assay for the alternative complement pathway activity assessment (AP100).

Since the introduction of the most expensive drug in the world (Eculizumab) in the therapeutic arsenal of many diseases involving the alternative complement pathway (ACP) in their pathophysiology, the unmet need to perform simple ACP assays affordable for all countries has become one of the major challenges of the contemporary medicine. The assay currently used is AH50, despite it still challenging for several laboratories. This educational chapter consists of a detail protocol of standardized hemolytic assay AP100 and aims to help clinical laboratories over the world and especially those of the developing and low income countries to perform it. The procedure is essentially the same as for the timed lysis assay and dilution methods (AP50) except the concentration of ACP buffer and the chicken erythrocyte density used to make the gels. In clinical field, AP100 has at least nine applications in disease diagnosis and follow-up. AP100 has many advantages over the AH50 as it is more reliable for the Eculizumab monitoring and more practical with a purpose to be stored and transported for several weeks. AP100 is a portable and easy to use device both at the bedside and in the companion medical care.

Complementology's foundation: The 100-year anniversary of the Nobel Prize to Jules Bordet.

The discovery of the complement system was associated with the creation of medical serodiagnosis in the early 20th century. Its biotechnological applications, usable even a century after its development by Jules Bordet, preceded for decades the proof of its biochemical rather than biophysical nature. Complement science has begun to emerge, thanks to the labs of Michael Heidelberger and his student Manfred Martin Mayer. Complementology had known difficult moments like the suicide of Louis Pillemer by swallowing the reagents of his laboratory following the criticisms of his discovery by Robert A. Nelson, Jr., in March 1957, at the Walter Reed Army Institute. This alternative complement pathway continues to revolutionize medicine by its implications as the principal component of immunosurveillance and as an amplification loop for plasma proteolytic cascades. Moreover, the drug designed in pathologies related to this pathway, eculizumab, was the most expensive drug in the world at the beginning of its marketing. Complementology promises great hopes in inflammatory and degenerative diseases, regenerative medicine, transplantation, and vector nanotechnology and as a diagnostic tool primarily in transplantation and inflammatory imaging. The moral and historical responsibility requires to make known this legacy to the new generation of doctors and scientists and also the technicians of the clinical laboratory of complementology throughout the world.

C3:CH50 ratio as a proposed composite marker for eculizumab monitoring in atypical hemolytic uremic syndrome: Preliminary results.

Treatment of atypical hemolytic uremic syndrome (aHUS) by the complement C5 inhibitor eculizumab (Soliris®) is highly effective but unfortunately, associated with an economic pressure on the health care systems even in high incomes countries. Despite spacing infusions having been proposed as the unique solution to minimize this economic impact, no reliable laboratory assays are available to tailor such therapy optimization. We aimed to propose and evaluate a complement composite marker for eculizumab efficacy monitoring in aHUS. We have retrospectively analyzed complement profiles data of eight aHUS patients under eculizumab from the International Registry of HUS/Thrombotic Thrombocytopenia Purpura, and calculated a novel marker "C3:CH50 ratio" by dividing C3 value by CH50 one for each sample during induction and maintenance periods. The results significance was compared to the currently used biomarkers for eculizumab tailoring. In contrast to the current biomarkers used for eculizumab efficacy monitoring like CH50 and soluble or deposit membrane attack complexes, "C3:CH50 ratio" seems to be the most interesting one since its value at pre-eculizumab dosage equaled 0.92 ± 0.2 while the post-eculizumab one increased significantly to reach 24.54 ± 10.7; P < 0.001. Furthermore, this ratio correlated negatively with platelets count (r = -0.722, P = 0.018) while no correlation was found within the thrombotic microangiopathy (TMA) biomarkers and complement blockade for the other parameters that change in pre and post-eculizumab therapy. As far as we know, this is the first study that suggests a post-eculizumab parameter correlating simultaneously with drug's activity (complement inhibition) and disease activity (platelets counts). Nonetheless, the limited number of patients enrolled in this study should be considered in larger studies to guide eculizumab optimization by indicating the time when subsequent withdrawal or infusion spacing is allowed or recommended.