Janko Pejovic

Immune Complexes and Complement in Serum and Synovial Fluid of Rheumatoid Arthritis Patients

Immune Complexes and Complement in Serum and Synovial Fluid of Rheumatoid Arthritis Patients Rheumatoid arthritis (RA) is predominantly an intraarticular inflammatory and autoimmune disease that involves different autoantibodies and effector mechanisms. The aim of the study was to determine the utility of Circulating Immune Complexes (CIC) and complement components (C3c, C4) as possible markers for the disease activity in laboratory diagnostics. In a cross-section study 59 patients, according to the clinical criteria, were categorized into two groups: group with moderate (MA, n=24), and group with severe activity (SA, n=35) of RA. The concentration of CIC, C3c and C4 in sera (S) and synovial fluids (SF) was examined by an immunonephelometric method in both groups and compared with values in the control group (n=15) of patients with lesions of the menisci. Obtained results showed that there was no statistical significance in the values of C3c and C4, in both biological fluids, among all tested groups. Significant differences were found in the levels of CIC in both fluids, while testing the parameters (× ± SD, IU/mL) in the sera of groups with SA and MA of RA: 7.43 ± 13.40; 3.01 ± 2.92 (p<0.05) and SF: 13.47 ± 21.1, 5.33 ± 7.53 (p<0.001), respectively. These differences were higher between the group with SA and CG. Results for the concentrations of CIC were significantly higher in SF compared to sera: in the RA group with SA by 77% and group with MA by about 82%. These data could provide a confirmation of the hypothesis about local, intraarticular autoantibodies and subsequent CIC production. It can be concluded that the examination of CIC concentration in serum, and where it is possible in SF, is a useful marker of disease activity in RA patients, in contrast to the tested components of the complement. This statement does not exclude their consumption within immune effector mechanisms, but elicits the possibility that lower molecular fragments (C3d, C4d), as well as the novel activation products, could be better disease activity markers in RA patients. Imunski Kompleksi i Komplement u Serumu i Sinovijalnoj Tečnosti Kod Bolesnika sa Reumatoidnim Artritisom Reumatoidni artritis (RA) jeste predominantno intraartikularna zapaljenska i autoimunska bolest u koju su uključena različita autoantitela i efektorni mehanizmi. Cilj ispitivanja je bio da se ustanovi značaj cirkulišućih imunskih kompleksa (CIK) i komponenti komplementa (C3c, C4), kao pokazatelja stepena aktivnosti RA za laboratorijsku dijagnostiku. U studiji preseka stanja je ispitano 59 bolesnika koji su prema kliničkim kriterijumima za aktivnost RA podeljeni u dve grupe: grupu sa umerenom (UA, n=24) i grupu sa visokom aktivnošću (VA, n=35) RA. Koncentracije CIK, C3c i C4 u serumu i sinovijalnoj tečnosti (ST) određivane su imunonefelometrijskom metodom u obe grupe ispitanika i upoređene sa vrednostima u kontrolnoj grupi od 15 pacijenata s povredama meniskusa. Rezultati su pokazali da nije bilo statistički značajnih razlika u koncentracijama za C3c i C4 u oba biološka uzorka između ispitivanih grupa. Statistički značajne razlike u koncentracijama CIK utvrđene testiranjem vrednosti (× ± SD, IU/mL) u serumu između grupe sa VA i grupe sa UA RA bile su: 7,43 ± 13,40; 3,01 ± 2,92 (p < 0,05) i za vrednosti u ST: 13,47 ± 21,1, 5,33 ± 7,53 (p < 0,001). Razlike su bile više izražene između grupe sa VA RA i KG. Rezultati koncentracija CIK su bili značajno viši u ST u odnosu na serum u obe grupe bolesnika: u grupi sa UA za 77% a u grupi sa VA RA za 82%. Ti podaci idu u prilog potvrdi hipoteze o lokalnoj, intraartikularnoj produkciji autoantitela, odnosno CIK. Može se zaključiti da je laboratorijsko određivanje koncentracije CIK korisan pokazatelj stepena aktivnosti RA, što se ne odnosi na ispitivane komponente komplementa. To ne isključuje njihovu aktivnost u okviru efektornog imunskog mehanizma, ali ukazuje na to da bi manji molekulski fragmenti (C3d, C4d) i novi aktivacioni produkti mogli biti bolji pokazatelji stepena aktivnosti RA.

N-Terminal Pro-B-Type Natriuretic Peptide in Patients with Hypertensive Heart Disease

N-Terminal Pro-B-Type Natriuretic Peptide in Patients with Hypertensive Heart Disease Patients with hypertensive heart disease have elevated concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP). The aim of our study was to evaluate NT-proBNP in patients with long-standing hypertension and in patients with signs of hypertensive cardiomyopathy. The study included three groups of 50 subjects: healthy persons (Control Group), patients with hypertension and normal left ventricular systolic function (Group 1) and patients with longstanding hypertension and signs of hyper tensive cardiomyopathy with impaired left ventricular systolic function (Group 2). Our results show a very good correlation (Pearsons test) between NT-proBNP in Group 1 and Group 2 and C-reactive protein (Group 1: r = 0.8424; Group 2: r = 0.6650), systolic blood pressure (Group 1: r = 0.7213; Group 2: r = 0.4856), diastolic blood pressure (Group 1: r = 0.4282; Group 2: r = 0.3989) and ejection fraction (Group 1: r = -0.7390; Group 2: r = 0.9111). ROC analysis revealed that the AUC between the Control Group and Group 1 for NT-proBNP (0.912) was not significantly different (p>0.05) from the AUC for systolic (0.924) and diastolic pressure (0.937). A cut-off value for NT-proBNP of 5.89 pmol/L can be used to reliably distinguish patients of Group 1 from the Control Group, and a cut-off value of 21.67 pmol/L reliably separates patients from Group 1 and Group 2 (in both cases, the AUC is 1.000). Patients in Group 2 who belonged to the II and III New York Heart Association (NYHA) class had significantly higher levels of NT-proBNP than those in NYHA class I (ANOVA test, p=0.001). These data suggest that NT-proBNP is a useful biomarker for distin guishing patients with long-standing hypertension who are at risk of heart failure, allowing optimization and proper treatment of these patients. N-Terminalni Pro-B-Tip Natriuretskog Peptida Kod Pacijenata sa Hipertenzivnim Srčanim Oboljenjima Pacijenti sa hipertenzivnim srčanim oboljenjima imaju povišene koncentracije N-terminalnog pro-B-tipa natriuretskog peptida (NT-proBNP). Cilj rada bio je da se izvrši evaluacija razlika u NT-proBNP kod pacijenata sa dugogodišnjom arterijskom hipertenzijom i znacima hipertenzivne kardiomiopatije. Ispitivanje je obuhvatilo tri grupe sa po 50 ispitanika: zdrave osobe (kontrolna grupa), pacijente sa arterijskom hipertenzijom i normalnom sistolnom funkcijom leve komore (grupa 1) i pacijente sa dugogodišnjom arterijskom hipertenzijom i znacima hipertenzivne kardiomiopatije sa oslabljenom sistolnom funkcijom leve komore (grupa 2). Dobijeni podaci pokazali su da NT-proBNP u grupi 1 kao i u grupi 2 veoma dobro koreliše (Pearsonov test) sa CRP (grupa 1: r = 0,8424; grupa 2: r = 0,6650), sistolnim pritiskom (grupa 1: r = 0,7213; grupa 2: r = 0,4856), dijastolnim pritiskom (grupa 1: r = 0,4282; grupa 2: r = 0,3989) i ejekcionom frakcijom (grupa 1: r = -0,7390; grupa 2: r = 0,9111). ROC analiza je pokazala da se AUC izme u kontrolne grupe i grupe 1 za NT-proBNP (0,912) značajno ne razlikuje (p > 0,05) od AUC za sistolni (0,924) i dijastolni pritisak (0,937). Na osnovu cutoff vrednosti za NT-proBNP od 5,89 pmol/L mogu se pouzdano razlikovati pacijenti u grupi 1 od kontrol ne grupe, dok se pomoću cutoff vrednosti od 21,67 pmol/L pouzdano razdvajaju pacijente iz grupe 1 i grupe 2 (u oba slučaja AUC su 1,000). Pacijenti u grupi 2 koji su pripadali II i III New York Heart Association (NYHA) klasi su imali značajno više vrednosti NT-proBNP od onih u I NYHA klasi (ANOVA test, p = 0,001). Ovi podaci ukazuju na to da je NT-proBNP koristan biomarker za razlikovanje pacijenata sa dugogodišnjom arterijskom hipertenzijom kojima preti zastojna srčana slabost, što omogućava optimizaciju i adekvatan tretman ovih pacijenata.

Subcutaneous adipose tissue measurements and better metabolic prediction

The aim of the study was to establish the importance of an additional measurement of subcutaneous adipose tissue thickness (SAT) on a predetermined position on the waistline, and its relation to waist measurements as an improvement of metabolic prediction in equally obese subjects. One hundred and forty two consecutive patients were enrolled in the study: stratified by weight as normal (body mass index — BMI 20–25 kg/m2), overweight (BMI 25–30 kg/m2) and obese (BMI >30 kg/m2); and by fasting glucose level as normoglycemic, impaired fasting glucose (IFG), or with type 2 diabetes mellitus (T2DM). SAT was measured in relaxed expiration, 3 cm left of the umbilicus, with ultrasound. Fasting blood samples for glucose, insulin and HbAlc were taken. Waist circumference was slightly higher in the IFG (112.8 cm) and normoglycemic groups (115.62 cm), compared to T2DM (108.15 cm). The T2DM group had a lower average SAT (2.7 cm) than both the IFG group (3.4 cm, p<0.01) and the normoglycemic group (4.2cm, p=0.001). The homeostatic model of assessment for insulin resistance (HOMA IR) was the lowest in normoglycemic and the highest in IFG group. Waistline radius to SAT ratio provides better insight into the deterioration of glucose metabolism than standard anthropometric markers of abdominal obesity in equally obese patients.

Prognostic Value And Daily Trend Of Interleukin-6, Neutrophil CD64 Expression, C-Reactive Protein And Lipopolysaccharide-Binding Protein In Critically Ill Patients: Reliable Predictors Of Outcome Or Not?

Summary Background: Severe sepsis and/or trauma complicated by multiple organ dysfunction syndrome are the leading causes of death in critically ill patients. The aim of this prospective single-centre study was to assess the prognostic value and daily trend of interleukin-6 (IL-6), neutrophil CD64 expression, C-reactive protein (CRP) and lipopolysaccharide-binding protein (LBP) regarding outcome in critically ill patients with severe trauma and/or severe sepsis. Outcome measure was hospital mortality. Methods: One hundred and two critically ill patients admitted to the intensive care unit of a tertiary university hospital were enrolled in this prospective study. Blood samples were collected on admission (day 1), days 2 and 3. Results: CD64 index was 1.6-fold higher on day 1 and 1.78-fold higher on day 2 in non-survivors (p<0.05). The area under the curve (AUC) for the CD64 index on day 1 for outcome was 0.727. At a cut-off level of 2.80 sensitivity was 75% and specificity was 65%. Patients with CD64 index level on day 1 higher than 2.80 had 2.4-fold higher probability of dying. Odds ratio is 2.40; 95% CI 0.60–9.67. Conclusions: CD64 index on day 1 is a fairly good predictor of outcome. AUCs for IL-6, CRP and LBP were < 0.55, suggesting these biomarkers failed to predict outcome.

Free Light Chains of Immunoglobulin as a Prognostic Factor for Some Plasmaproliferative Diseases

Free Light Chains of Immunoglobulin as a Prognostic Factor for Some Plasmaproliferative Diseases Quantitation of monoclonal immunoglobulins and their fragments is used for monitoring the plasmaproliferative disease course and the effect of therapy. The aim of free light chains examination was to evaluate the significance of the FLC ratio as a prognostic factor for remission, progression and survival in different disease groups. The concentrations of immunoglobulins and free light chains were measured by an immunonephelometric method on a »SIEMENS« DADE BN II analyser with reagents (Freelite, The Binding Site, UK). In this examination 151 patients from 3 different disease groups: 1. Light chain disease or Bence Jones myeloma (37), 2. Biclonal gammopathy with FLC (23) and 3. Monoclonal gammopathy of undetermined significance (91), were investigated during a period of 7 years. The reference interval for FLC ratio is 0.26-1.65. According to the International Staging System for multiple myeloma, a serum FLC ratio of <0.03 or >32 was taken as abnormal. The patients with light chain disease and biclonal gammopathy with FLC with an abnormal FLC ratio and a combination of adverse risk factors (76.7%) had median survival times of 22-30 months, versus patients with a normal or slightly varied FLC ratio without adverse risk factors (23.3%) with median survival times of 39-51 months. About 38% of patients who had shown lowered free light chains values by more than 50% under therapy, achieved disease remission in the light chain disease and biclonal gammopathy with FLC groups. In the group of patients with monoclonal gammopathy of undetermined significance, 66.0% had a normal or slightly modified FLC ratio which corresponds to low and low-intermediate risk of disease progression, as opposed to 34.0% with an abnormal FLC ratio (<0.25 or >4) which corresponds to high and high-intermediate risk. An abnormal FLC ratio in the examined groups could be an independent risk factor for progression and poorer disease prognosis. Slobodni Laki Lanci Imunoglobulina Kao Prognostički Faktor Kod Nekih Plazmaproliferativnih Bolesti Kvantitativno određivanje monoklonskih imunoglobulina i njihovih fragmenata koristi se za praćenje toka i terapijskog odgovora kod plazmaproliferativnih bolesti. Cilj određivanja slobodnih lakih lanaca imunoglobulina u serumu bolesnika jeste provera značaja njihovog količnika (κ/λ indeks) kao prognostičkog faktora remisije, progresije i preživljavanja. Koncentracije imunoglobulina i slobodnih lakih lanaca određivane su imunonefelometrijskom metodom na analizatoru SIEMENS DADE Behring II sa reagensima (FREELITE, The Binding Site, UK). U ispitivanje je uključen 151 bolesnik tokom perioda od 7 godina, koji su razvrstani u 3 grupe: 1. bolest lakih lanaca ili Bence Jones mijelom (37); 2. biklonalna gamapatija sa slobodnim lakim lancima (23) i 3. monoklonska gamapatija neutvrđenog značaja (91). Referentnim intervalom za κ/λ indeks smatraju se vrednosti 0,26-1,65. Prema Internacionalnom prognoznom indeksu za multipli mijelom, kao patološki uzet je κ/λ indeks <0,03 ili >32. Bolesnici iz prve dve grupe sa patološkim k/λ indeksom i kombinacijom nepovoljnih faktora rizika (76,7%) imali su prosečno vreme preživljavanja 22-30 meseci, nasuprot bolesnicima sa fiziološkim ili neznatno izmenjenim κ/λ indeksom bez nepovoljnih faktora rizika (23,3%), sa prosečnim vremenom preživljavanja 39-51 mesec. Oko 38% bolesnika koji su pod terapijom imali sniženje κ/λ indeksa >50% su ostvarili remisiju bolesti. U grupi ispitanika sa MGNZ, 66,0% je imalo fiziološke ili neznatno izmenjene κ/λ indekse, što odgovara niskom i srednje niskom riziku progresije, nasuprot 34,0% sa patološkim κ/λ indeksom (<0,25 ili >4), što odgovara srednje visokom i visokom riziku progresije. Postojanje patološki značajnog κ/λ indeksa u ispitivanim grupama predstavlja nezavisan faktor rizika za progresiju bolesti i lošiju prognozu.