Evaluation of circulating immune complexes and antiphospholipid antibodies (anti beta 2 glycoprotein 1) in heroin addicts and their clinical significance

NTRODUCTION: Earlier studies have reported that heroin might cause the structural and antigen changes on numerous tissues, organs and subsequent development of autoimmune reactions (production of antibodies and creation of immune complexes) as a result the immunotoxic effect of heroin. The aims of our study were to: a) Evaluate CIC and antibeta2GP1 in heroin addicts; b) Correlate between the values of the obtained CIC and antibeta2GP1 (stratified by the duration and route of heroin application); c) Compare the CIC and antibeta2GP1 in heroin addicts and the control group and d) Assess the clinical importance of CIC and antibeta2GP1 in heroin addicts. PATIENTS AND METHODS: This was a cross-sectional study performed at the University Clinic of Toxicology and the Institute of Transfusiology, Skopje, Republic of Macedonia. Patients referred to the Clinic for clinical examinations who met the inclusion criteria were analyzed. Protocol for work was the following: 1.) detailed anamnestic data, 2.) a whole set of laboratory biochemical blood and urine analyses, 3.) examination with the Schiller's twelve-channel ECG; 4.) toxicological analyses for opioids in a urine sample; circulating immune complexes and 5.) antiphospholipid antibodies (antibeta2GP1, fractions: IgA, IgG, IgM). The obtained results were statistically analyzed. RESULTS: We included 37 heroin addicts and a control group of 27 healthy subjects. Male abusers predominated over female in--28 (76%) subjects; mean age being 26 +/- 5.06. The results which refer to the increased values of circulating immune complexes have shown a high statistically significant dominance of heroin addicts, in comparison with the control group (p < 0.01) and increased values above the reference ones of IgG antibeta2GP1, alone in the group of intravenous heroin abusers (p < 0.025). The mean duration of the heroin use in intravenous abusers was 6.21 +/- 3.25 years, whereas in those snorting heroin was 5.15 +/- 2.26 years. Duration of heroin application was in a positive correlation with IgG antibeta2GP1 (p = 0.35). CONCLUSIONS: Our data showed that heroin-dependent patients in our study had increased values of circulating immune complexes and changes in IgG and IgM antibeta2GP1 with significantly increased values of IgG antibeta2GP1 in the intravenous heroin abusers. The duration of heroin application is in direct proportional relationship with IgG antibeta2GP1. Heroin addicts had significantly higher values of circulating immune complexes and statistically significant difference in IgG antibeta2GP1, in comparison with the control group. Changes in the fractions of antibeta2GP1 and CIC suggest a possible relation with the somatic changes found in heroin addicts (i.e. thrombocytopenia, reduced renal clearance, etc)

Changes of some humoral immunologic indicators an clinical manifestations cryoglobulinemia in heroin addicts

Different autoantibodies and immunologic abnormalities have been described in heroin addicts. AIMS: dpending on the route of heroin application in heroin addicts to determine: 1) immunoglobulins: IgA, IgG, IgM; 2) complement (C3, C4); 3) some other autoantibodies RF, anti β2GP1 fractions: IgA, IgG, IgM, ANA; 4) CIC; 5)monitoring the cryoglobulin presence; 6) clinical manifestations in cryoglobulin positive heroin addicts. A total of 363 heroin addicts were analyzed after previously completed questionnaire; biochemical analyses of blood and urine; creatinine clearance (eC(Cr)) by Cockcroft-Gault formula; proteinuria; 24-hour proteinuria (Uprot/Ucreat); ECG; toxicological analyses; complement (C3, C4); immunoglobulins IgA, IgG, IgM; rheumatoid factor; cryoglobulins; circulating immune complexes; antiphospholipid antibodies (anti β2GP1: IgA, IgG, IgM); antinuclear antibodies. Male patients were predominating (82.09%). Of them 161 were using intravenous heroin (45.4%). IgA was statistically significantly lower in intravenous heroin addicts. Intravenous heroin addicts contrary to those who inhaled heroin had highly significant levels of IgG, IgM, IgG, antiβ2GP1 cryoglobulins; significantly higher mean values of: RF, anti β2GP1 IgA and IgM. Cryoglobulin positive (CP) heroin addicts compared to cryoglobulin negative (CN) presented significantly more frequently with clinical signs of arthralgia, vasculitis, hematuria; whereas highly significantly were manifested respiratory difficulties, neurological disorders, Raynaud phenomenon, proteinuria, 24-hour proteinuria, highly significantly lower mean values of renal clearance. Intravenous heroin addicts compared to the non-parenteral heroin addicts have shown greater changes in certain parameters of humoral immunity. CP heroin addicts have presented with more frequent clinical manifestations than CN heroin addicts

The presence of some humoral immunologic indicators and clinical manifestations in cryoglobulin positive heroin addicts without evidence of hepatitis virus infection

Introduction. Cryoglobulins are single or mixed immunoglobulins that are subject to reversible precipitation at low temperatures. Objective. The aims of this paper were: 1. Comparison of cryoglobulin positive (CP), cryoglobulin negative (CN) heroin addicts and the control group (CG) in terms of serum immunoglobulins IgG, IgA and IgM and complement components C3 and C4; 2. Comparison of CP and CN heroin addicts in terms of rheumatoid factor (RF) and circulating immune complexes (CIC); 3. Assessment of clinical manifestations in CP heroin addicts. Methods. This is a comparative study of cases (outpatients) treated at the University Clinic of Toxicology in Skopje over 3.5 years, from January 2009 to June 2012. In this study 140 heroin addicts without HbsAg were examined, seronegative for HCV and HIV infections. They were divided into 2 groups: 70 CP and 70 CN heroin addicts. A previously designed self-administered questionnaire was used as a data source on participants. All heroin addicts underwent the following analyses: urea and creatinine in serum; creatinine in urine; proteinuria; 24-hour proteinuria; IgM, IgG, IgA, C3, C4 ; RF; CIC; creatinine clearance; ECG; toxicological analyses for opioids in a urine sample; cryoglobulins. In addition to these 2 groups, IgG, IgA, IgM, C3 and C4 were also examined in 70 healthy subjects (CG). Results. The study showed that there was no statistically significant difference between CP, CN heroin addicts and CG regarding the concentration of IgA, IgG, IgM, C3 and C4, and between CP and CN regarding the concentration of CIC. There was significant difference between CP and CN regarding the concentration of RF. The following conditions were significantly more frequently manifested in CP than in CN heroin addicts: arthralgia, Raynaud’s phenomenon, respiratory difficulties, neurological disorders, manifested skin changes, hematuria, 24-hour proteinuria levels, and decreased renal clearance. Conclusion. There were no differences in concentrations of IgG, IgA, IgM, C3, C4 and CIC, while there was a difference in concentration of RF between CP and CN heroin addicts. Clinical manifestations (arthralgias, Raynaud’s phenomenon, respiratory, neurologic, renal disorders and skin changes) were more common in CP heroin addicts

Evaluation of circulating immune complexes and antiphospholipid antibodies ( anti beta 2 glycoprotein 1) in heroin addicts and their clinical significance

NTRODUCTION: Earlier studies have reported that heroin might cause the structural and antigen changes on numerous tissues, organs and subsequent development of autoimmune reactions (production of antibodies and creation of immune complexes) as a result the immunotoxic effect of heroin. The aims of our study were to: a) Evaluate CIC and antibeta2GP1 in heroin addicts; b) Correlate between the values of the obtained CIC and antibeta2GP1 (stratified by the duration and route of heroin application); c) Compare the CIC and antibeta2GP1 in heroin addicts and the control group and d) Assess the clinical importance of CIC and antibeta2GP1 in heroin addicts. PATIENTS AND METHODS: This was a cross-sectional study performed at the University Clinic of Toxicology and the Institute of Transfusiology, Skopje, Republic of Macedonia. Patients referred to the Clinic for clinical examinations who met the inclusion criteria were analyzed. Protocol for work was the following: 1.) detailed anamnestic data, 2.) a whole set of laboratory biochemical blood and urine analyses, 3.) examination with the Schiller's twelve-channel ECG; 4.) toxicological analyses for opioids in a urine sample; circulating immune complexes and 5.) antiphospholipid antibodies (antibeta2GP1, fractions: IgA, IgG, IgM). The obtained results were statistically analyzed. RESULTS: We included 37 heroin addicts and a control group of 27 healthy subjects. Male abusers predominated over female in--28 (76%) subjects; mean age being 26 +/- 5.06. The results which refer to the increased values of circulating immune complexes have shown a high statistically significant dominance of heroin addicts, in comparison with the control group (p < 0.01) and increased values above the reference ones of IgG antibeta2GP1, alone in the group of intravenous heroin abusers (p < 0.025). The mean duration of the heroin use in intravenous abusers was 6.21 +/- 3.25 years, whereas in those snorting heroin was 5.15 +/- 2.26 years. Duration of heroin application was in a positive correlation with IgG antibeta2GP1 (p = 0.35). CONCLUSIONS: Our data showed that heroin-dependent patients in our study had increased values of circulating immune complexes and changes in IgG and IgM antibeta2GP1 with significantly increased values of IgG antibeta2GP1 in the intravenous heroin abusers. The duration of heroin application is in direct proportional relationship with IgG antibeta2GP1. Heroin addicts had significantly higher values of circulating immune complexes and statistically significant difference in IgG antibeta2GP1, in comparison with the control group. Changes in the fractions of antibeta2GP1 and CIC suggest a possible relation with the somatic changes found in heroin addicts (i.e. thrombocytopenia, reduced renal clearance, etc)

The Presence of Some Humoral Immunologic Indicators and Clinical Manifestations in Cryoglobulin Positive Heroin Addicts without Evidence of Hepatitis Virus Infection

INTRODUCTION: Cryoglobulins are single or mixed immunoglobulins that are subject to reversible precipitation at low temperatures. OBJECTIVE: The aims of this paper were: 1. Comparison of cryoglobulin positive (CP), cryoglobulin negative (CN) heroin addicts and the control group (CG) in terms of serum immunoglobulins IgG, IgA and IgM and complement components C3 and C4; 2. Comparison of CP and CN heroin addicts in terms of rheumatoid factor (RF) and circulating immune complexes (CIC); 3. Assessment of clinical manifestations in CP heroin addicts. METHODS: This is a comparative study of cases (outpatients) treated at the University Clinic of Toxicology in Skopje over 3.5 years, from January 2009 to June 2012. In this study 140 heroin addicts without HbsAg were examined, seronegative for HCV and HIV infections.They were divided into 2 groups: 70 CP and 70 CN heroin addicts. A previously designed self-administered questionnaire was used as a data source on participants. All heroin addicts underwent the following analyses: urea and creatinine in serum; creatinine in urine; proteinuria; 24-hour proteinuria; IgM, IgG, IgA, C3, C4; RF; CIC; creatinine clearance; ECG; toxicological analyses for opioids in a urine sample; cryoglobulins. In addition to these 2 groups, IgG, IgA, IgM, C3 and C4 were also examined in 70 healthy subjects (CG). RESULTS: The study showed that there was no statistically significant difference between CP, CN heroin addicts and CG regarding the concentration of IgA, IgG, IgM, C3 and C4, and between CP and CN regarding the concentration of CIC. There was significant difference between CP and CN regarding the concentration of RF. The following conditions were significantly more frequently manifested in CP than in CN heroin addicts: arthralgia, Raynaud's phenomenon, respiratory difficulties, neurological disorders, manifested skin changes, hematuria, 24-hour proteinuria levels, and decreased renal clearance. CONCLUSION: There were no differences in concentrations of IgG, IgA, IgM, C3, C4 and CIC, while there was a difference in concentration of RF between CP and CN heroin addicts. Clinical manifestations (arthralgias, Raynaud's phenomenon, respiratory, neurologic, renal disorders and skin changes) were more common in CP heroin addicts

The presence of some humoral immunologic indicators and clinical manifestations in cryoglobulin positive heroin addicts without evidence of hepatitis virus infection

Different autoantibodies and immunologic abnormalities have been described in heroin addicts. AIMS: dpending on the route of heroin application in heroin addicts to determine: 1) immunoglobulins: IgA, IgG, IgM; 2) complement (C3, C4); 3) some other autoantibodies RF, anti β2GP1 fractions: IgA, IgG, IgM, ANA; 4) CIC; 5)monitoring the cryoglobulin presence; 6) clinical manifestations in cryoglobulin positive heroin addicts. A total of 363 heroin addicts were analyzed after previously completed questionnaire; biochemical analyses of blood and urine; creatinine clearance (eC(Cr)) by Cockcroft-Gault formula; proteinuria; 24-hour proteinuria (Uprot/Ucreat); ECG; toxicological analyses; complement (C3, C4); immunoglobulins IgA, IgG, IgM; rheumatoid factor; cryoglobulins; circulating immune complexes; antiphospholipid antibodies (anti β2GP1: IgA, IgG, IgM); antinuclear antibodies. Male patients were predominating (82.09%). Of them 161 were using intravenous heroin (45.4%). IgA was statistically significantly lower in intravenous heroin addicts. Intravenous heroin addicts contrary to those who inhaled heroin had highly significant levels of IgG, IgM, IgG, antiβ2GP1 cryoglobulins; significantly higher mean values of: RF, anti β2GP1 IgA and IgM. Cryoglobulin positive (CP) heroin addicts compared to cryoglobulin negative (CN) presented significantly more frequently with clinical signs of arthralgia, vasculitis, hematuria; whereas highly significantly were manifested respiratory difficulties, neurological disorders, Raynaud phenomenon, proteinuria, 24-hour proteinuria, highly significantly lower mean values of renal clearance. Intravenous heroin addicts compared to the non-parenteral heroin addicts have shown greater changes in certain parameters of humoral immunity. CP heroin addicts have presented with more frequent clinical manifestations than CN heroin addicts

DE NOVO ANTI HLA ANTIBODIES AFTER KIDNEY TRANSPLANTATION: CLINICAL SIGNIFICANCE AND ASSOCIATION WITH GRAFT FUNCTION

Background. Kidney transplantation (TR) is the best treatment of chronic kidney disease. Chronic cellular and antibody mediated rejections have still major impact on graft survival. Single antigen bead technology enabled detection of donor specific (DSA) and non-donor specific (Non-DSA) anti HLA antibodies (HLA-Ab). Our study investigates the impact of de novo HLA-Ab on graft function (GF) 12 months after TR. Material and methods. 50 pts with living (42) and deceased donor (8) transplantation were included in a 12-month prospective study. HLA-Ab were analyzed using LABScreen mixed kit in the 1st and 12th month after TR. According to the presence of HLA-Ab, pts were divided in group 1 (HLA+) and group 2 (HLA -). Both groups did not differ regarding gender, age, living or deceased donor, immunosuppression, underlying renal disease, rejection episodes, HLA mismatch, cold and warm ischemia time. Serum creatinine (SCr), GFR (Cockroft Gault) and proteinuria (Pr) were analyzed 1st and 12th month after TR. Results. HLA-Ab were detected in 17 pts (34%), 5 with DSA (10%) and 12 with Non-DSA (24%). Group 1 has a significant worsening of GFR (SCr increased from 112.1 to 141.5 ( p<0.002) compared with the group 2 where SCr decreased from 116.4 to 111.31 µol/L.( p<0.23). In the same time GFR decreased from 69.7 to 57.09 and increased from 67.8 to 69.3 while Pr increased from 0.42 to 0.58 ( p< 0.26) and decreased from 0.81 to 0.32 ( p<0.051) in the groups 1 and 2, respectively. Conclusion. De novo DSA and Non-DSA produce graft injuries in the first 12 months after TR. Regular follow- up of HLA-Ab together with systematic protocol graft biopsy could be essential for further therapeutic interventions