scholarly journals Complement activation in individuals with previous subclinical Lyme borreliosis and patients with previous Lyme neuroborreliosis

Author(s):  
Hanna Carlsson ◽  
Kerstin Sandholm ◽  
Haben Woldu Haddish ◽  
Lars Brudin ◽  
Kristina Nilsson Ekdahl ◽  
...  

AbstractLyme borreliosis (LB) is caused by Borrelia burgdorferi and infection may lead to not only a large variety of clinical manifestations but also a subclinical outcome. The aim of the present study was to investigate if there is a constitutional difference in complement activation between individuals with previous subclinical Lyme borreliosis (SB) and patients previously diagnosed with Lyme neuroborreliosis (LNB).Lepirudin plasma for activation studies was collected from 60 SB individuals and from 22 patients pre-diagnosed with LNB. The plasma was incubated with live Borrelia spirochetes of two strains (complement sensitive B. garinii Lu59 and complement resistant B. afzelii ACA1).Complement factor C3 was measured in non-activated lepirudin plasma with immune-nephelometry and C3a and sC5b-9 generated during complement activation were measured by enzyme-linked immunosorbent assay.We found that the complement sensitive Lu59 induced higher complement activation than the complement resistant ACA1 when measuring activation products C3a and sC5b-9 in SB and LNB patients, p < 0.0001. No significant difference was found between SB and LNB patients in systemic levels of C3. Furthermore, SB individuals generated a higher activation of C3 cleavage to C3a (C3a/C3 ratio) than LNB patients after activation with ACA1, p < 0.001, but no significant differences were found in response to Lu59. In conclusion, Lu59 induced higher complement activation than ACA1 and individuals with previous SB showed increased generation of C3a compared with patients with previous LNB. In our study population, this mechanism could lead to less elimination of spirochetes in LNB patients and thereby be a factor contributing to the clinical outcome.

1987 ◽  
Author(s):  
A P Bode ◽  
D T Miller ◽  
S Newman

Platelets are routinely stored for transfusion at room temperature in autologous, citrated plasma. We have demonstrated previously that these conditions do not completely block activation of plasma enzyme systems, as indicated by generation of thrombin activity (Vox Sanguinis, JL1:192,1986). Here, we demonstrate the conversion of large amounts of complement factor C3 during storage of citrated PC by using radioimmunoassay quantitation of the activation peptide C3a des-Arg (Upjohn Diagnostics). Supernatant samples from stored PC and from citrated platelet-poor plasma (PPP) stored under the same conditions showed a rapid linear increase in C3a levels over time with no significant difference (paired t-test, p<0.5) between PC and PPP (see table). The values at Day 10 represent conversion of approximately 11% of the native C3. Possible effects on stored platelets of C3 conversion in the surrounding plasma include:activation of platelets by C3a des-Arg (M.Polley and R. Nachman; J.Exp.Med. 158:603, 1983) and deposition of C3b on the cell surface as "innocent bystanders" (A. Salama and C. Mueller-Eckhardt; Transfusion 25:528,1985).In contrast, <10 ng/mL C5a was found in all samples tested, representing less than 0.2%conversion of C5a.Nephelometricassay of native C5 levels in PC samples showed a slight but significant difference by a paired t-test (p=0.04) between fresh PC (mean=117 ug/mL±12.0, n=6)and P stored for 10 days(nean=108 ug/mL±9.7). Nochange in C5 levels was observed in stored PPP (106 ug/mL to 107 ug/mL). Radiolabelled monoclonal antibodies to C3 fragments showed less than 600 molecules bound per platelet. This study demonstrates for the first time the extent of complement activation in stored platelet concentrates.


2016 ◽  
Vol 11 ◽  
pp. BMI.S39053 ◽  
Author(s):  
Afzal Ahmad ◽  
Poornima Manjrekar ◽  
Charu Yadav ◽  
Ashish Agarwal ◽  
Rukmini Mysore Srikantiah ◽  
...  

AIM This study aimed at evaluation of ischemia-modified albumin (IMA), malondialdehyde (MDA), and advanced oxidative protein products (AOPP) as markers of vascular injury in diabetic nephropathy (DN) with derivation of cutoff values for the same. Materials and Methods Study population comprised 60 diabetes patients and 30 controls, with diabetes patients further categorized into three groups based on urine albumin/creatinine ratio (UACR) of <30 mg/g (diabetes without microalbuminuria), 30–300 mg/g (early DN), and >300 mg/g of creatinine (overt DN). Serum IMA, MDA, and AOPP were estimated by enzyme-linked immunosorbent assay; HbA1c, serum creatinine, urine albumin, and urine creatinine were estimated using automated analyzers. Statistical analysis was done using analysis of variance, Pearson's correlation coefficient, and receiver-operating characteristic curve. Results A statistically significant difference was found in the levels of IMA among patients with early DN (154 ng/mL), diabetes without nephropathy (109.4 ng/mL), and healthy controls (45.7 ng/mL), with highest levels in early DN cases. Similar increase was seen in AOPP as well. A significant correlation was observed between IMA and UACR in diabetes without nephropathy ( r = 0.448). Conclusion The present study postulates serum IMA as a novel biomarker for the assessment of disease progression in diabetes even before microalbuminuria, and a cutoff point ≥99 ng/mL can be used for detection of early DN.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Sha-Sha Tao ◽  
Yi-Lin Dan ◽  
Guo-Cui Wu ◽  
Qin Zhang ◽  
Tian-Ping Zhang ◽  
...  

Background. Recently, increasing studies have revealed that leptin is involved in the development of rheumatoid arthritis (RA). This study is aimed at exploring the association of leptin gene single nucleotide polymorphisms (SNPs) with susceptibility to RA in a Chinese population. Methods. We recruited 600 RA patients and 600 healthy controls from a Chinese population and analyzed their three leptin SNPs (rs10244329, rs2071045, and rs2167270) using the improved Multiplex Ligase Detection Reaction (iMLDR) assays. The associations of these SNPs with clinical manifestations of RA were also analyzed. Enzyme-linked immunosorbent assay (ELISA) was performed for plasma leptin determination. Results. No significant difference in either allele or genotype frequencies of these three SNPs between RA patients and healthy controls was observed (all P > 0.05 ). Association between the genotype effects of dominant, recessive models was also not found (all P > 0.05 ). No significant difference in plasma leptin levels was detected between RA patients and controls ( P > 0.05 ). Conclusion. Leptin gene (rs10244329, rs2071045, and rs2167270) polymorphisms are not associated with RA genetic susceptibility and its clinical features in the Chinese population.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Bo Bødker Jensen ◽  
Mie Topholm Bruun ◽  
Per Moestrup Jensen ◽  
Andreas Kristian Pedersen ◽  
Pierre-Edouard Fournier ◽  
...  

Abstract Background Various tick-borne infections like borreliosis and rickettsiosis pose a health risk to humans in many parts of the world. We investigated seroprevalence of and seroconversion to Borrelia burgdorferi and Rickettsia spp. and relation to tick-bites, weather and clinical manifestations in Denmark. Methods Blood donors were enrolled at the Hospital of Southern Jutland in June–July with follow-up November–February of 2018 and 2019. Blood samples were collected, and a questionnaire regarding tick bites, potential exposures and symptoms was completed at each visit. Samples were tested for presence of IgM and IgG antibodies directed against B. burgdorferi and Rickettsia spp. using R. helvetica and R. felis as antigens. Data were examined for correlation between tick bites, serological results, potential exposures and symptoms. Results Two-hundred and fourteen (93 follow-ups) and 130 (38 follow-ups) blood donors were included in 2018 and 2019, respectively. The total borrelia seroconversion rate was 6.3% (CI 2.1–10.5), while the prevalence of IgM and IgG antibodies was 7.8% (CI 4.9–10.6) and 6.7% (CI 4–9.3), respectively. Seroconversion to Rickettsia spp. was detected in one participant. Tick bites and seroconversion were not significantly associated with the reported unspecific symptoms, but unspecific symptoms were common in the study population. There was no significant difference in number of tick bites or seroconversion/prevalence between seasons with highly alternating weather. Conclusions Results suggest that weather conditions in an individual year have a limited impact. Anti-Borrelia-antibodies do not seem to persist in serum for several years. Rickettsiosis is of limited concern in Denmark. Graphic abstract


Author(s):  
Shrishti Dhar Prasad ◽  
Suprava Patel ◽  
Ajoy Kumar Behera ◽  
Dibakar Sahu ◽  
Seema Shah ◽  
...  

Aims: An early diagnosis of severity can be confidently judged by monitoring the serum biomarkers in patients with COVID-19. The study was thus aimed to explore the relationship of the inflammatory and immune biomarkers in predicting the severity of the disease. Study design: It is a retrospective observational study. Methodology: The study included 79 confirmed cases of COVID-19 who had complete clinical record for the analytical variables. All cases were assigned a total clinical score as per their clinical manifestations, associated co-morbidities and mortality outcome. Laboratory inflammatory and immune biomarkers at the time of admission were noted. Results: The mean age of the study population was 55.38 (1.69) years. The percentage of admission for males (67.1%) was twice that of females (32.9%). Serum LDH (p=0.003) and ferritin (0.019) levels were remarkably raised in severe form. Total clinical score denoted a positive correlation with the inflammatory biomarkers (p<0.001). IgM exhibited a significant negative trend with increasing clinical score (p<0.001) and CRP levels (p=0.022) of the patients. The multivariate analysis reflected that the total clinical score was significantly influenced by initial SpO2 values (0.011), serum ferritin (0.027), IgM (0.001) and C3 levels (0.044) in the COVID-19 patients. Lower serum C3 values significantly influenced the hospitalization duration in moderate cases (p=0.034) and total clinical score in severe cases (p=0.01). Conclusion: The findings of the study signified that besides serum ferritin, a serial and close monitoring of serum IgM with complement factor C3 would aid in early prediction of clinical severity and thus guide physicians to start effective management strategy.


Author(s):  
Cody Riggle ◽  
Catherine Brissette

Lyme borreliosis or Lyme disease affects thousands of people globally each year, and, with nervous system involvement, this disease can lead to the development of Lyme neuroborreliosis (LNB). If not diagnosed and treated properly, LNB can lead to serious life-long health implications for affected patients. The clinical manifestations and treatment regimens are relatively well-studied, but much remains unknown about the disease’s pathogenesis and epidemiology. In this review, the authors elucidate the knowns and unknowns of LNB.


Author(s):  
Rumeysa Omer-Cihangir ◽  
Ulku Baser ◽  
Canan Kucukgergin ◽  
Gokce Aykol-Sahin ◽  
Olivier Huck ◽  
...  

Background: The determination of the impact of risk factors such as smoking in periodontal disease development is of importance to better characterize the disease. However, its impact on host response remains unclear. This study aimed to evaluate the effects of tobacco smoking on GCF levels of neutrophil enzymes (myeloperoxidase (MPO), beta-glucuronidase (BGD), neutrophil elastase (NE) and periodontal parameters in healthy young adults with dental plaque biofilm-induced gingivitis. Methods: The study population consisted of 60 systemically healthy young adults (39 smokers (Sm) and 21 non-smokers (n-Sm)) diagnosed with plaque-induced gingivitis. The periodontal examination consisted of a plaque index (PI); gingival index (GI); probing depth (PD); bleeding on probing (BoP), and clinical attachment level (CAL). GCF MPO, BGD, and NE levels were determined by means of an enzyme-linked immunosorbent assay (ELISA). Results: PI, GI, and BoP were significantly increased in the Sm group (p < 0.05). PD and CAL showed no significant difference between Sm and n-Sm groups (p > 0.05). In GCF, MPO, BGD, and NE levels were significantly increased in Sm group (p < 0.05). NE levels showed a significant correlation with GI and BoP (p < 0.05 for both). Moreover, a positive correlation between BGD and NE levels (p < 0.05) was measured. Conclusions: It may be concluded that, even in young patients, tobacco consumption affects the host’s immune response related to gingival inflammation. It is, therefore, mandatory to inform young patients about the risk related to tobacco consumption for their gingival health.


1989 ◽  
Vol 61 (03) ◽  
pp. 409-414 ◽  
Author(s):  
M Rånby ◽  
G Nguyen ◽  
P Y Scarabin ◽  
M Samama

SummaryAn enzyme linked immunosorbent assay (ELISA) based on goat polyclonal antibodies against human tissue plasminogen activator (tPA) was evaluated. The relative immunoreactivity of tPA in free form and tPA in complex with inhibitors was estimated by ELISA and found to be 100, 74, 94, 92 and 8l% for free tPA and tPA in complex with PAI-1, PAI-2, α2-antiplasmin and C1-inhibitor, respectively. Addition of tPA to PAI-1 rich plasma resulted in rapid and total loss of tPA activity without detectable loss of ELISA response, indicating an immunoreactivity of tPA in tPA/PAI-1 complex of about l00%. Three different treatments of citrated plasma samples (acidification/reneutralization, addition of 5 mM EDTA or of 0.5 M lysine) prior to determination by ELISA all resulted in increased tPA levels. The fact that the increase was equally large in all three cases along with good analytical recovery of tPA added to plasffi, supported the notion that all tPA antigen present in plasma samples is measured by the ELISA. Analysis by ELISA of fractions obtained by gel filtration of plasma from a patient undergoing tPA treatment identified tPA/inhibitor complexes and free tPA but no low molecular weight degradation products of tPA. Determinations of tPA antigen were made at seven French clinical laboratories on coded and randomized plasma samples with known tPA antigen content. For undiluted samples there was no significant difference between the tPA levels found and those known to be present. The between-assay coefficient of variation was 7 to 10%. In conclusion, the ELISA appeared suited for determination of total tPA antigen in human plasma samples.


1986 ◽  
Vol 56 (03) ◽  
pp. 250-255 ◽  
Author(s):  
C Boyer ◽  
M Wolf ◽  
C Rothschild ◽  
M Migaud ◽  
J Amiral ◽  
...  

SummaryA new solid phase enzyme-linked immunosorbent assay (ELISA) was developed for the quantitation of human Factor VII antigen (F VII Ag), using a monospecific rabbit anti-F VII antiserum. Anti-F VII F(ab′)2 fragments were adsorbed to polystyrene plates. The binding of serial dilutions of control or test plasma, containing F VII, was detected by incubation with peroxidase-labeled anti- FV II IgG followed by the addition of hydrogen peroxyde and O-phenylenediamine. This ELISA is specific, sensitive (detection limit: 0.05%) and accurate (coefficient of variation: 1.5-4% for within- and 1.6-9% for between-assays). F VII coagulant activity (F VII C) and F VII Ag were determined in large populations of controls and patients. In normal plasma (n = 38), F VII Ag ranged from 83 to 117% and the correlation coefficient between F VII Ag and F VII C was 0.94. In patients with severe (F VII C inf. 1%) congenital F VII deficiency (n = 5), F VII Ag was undetectable in two cases (inf. 0.05%) and markedly reduced (0.35 to 5.6%) in the three other cases. In patients with liver cirrhosis (n = 15), F VII Ag ranged from 21 to 59% and was in good correlation with F VII C (r = 0.84). In dicoumarol treated patients (n = 15), the levels of F VII Ag ranged from 51% to 79% and a poor correlation (r = 0.52) with F VIIC was observed. In “compensated” DIC (n = 5), levels of F VII Ag varied from 60 to 186%, with significantly higher F VII C levels (from 143 to 189%). In contrast, in “decompensated” DIC (n = 7), low F VII Ag and F VII C levels were observed (from 7 to 27%). In patients with deep-vein thrombosis (n = 25), high levels of F VII Ag (from 102 to 136%) and F VII C (from 110 to 150%) were demonstrated. In surgical patients, no significant difference was observed before and one day after intervention.


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