CH50 Levels Research Articles

Type B insulin resistance syndrome induced by increased activity of systemic lupus erythematosus in a hemodialysis patient

A-23-year-old woman with systemic lupus erythematosus (SLE) and on hemodialysis for 5 years was admitted to the hospital because of severe general fatigue. On admission, laboratory findings showed that fasting plasma glucose levels ranged from 25 â 45 mg/dl, a test for antinuclear antibody (ANA) was positive (1 : 320, with a discrete-speckled pattern), serum C3 and C4 complement and CH50 level were remarkably depressed (22.5 mg/dl, < 5.1 mg/dl, < 13 U/ml, respectively), and insulin receptor antibodies were present (89.3% inhibition of 125I-insulin binding to cultured human lymphocytes by a binding inhibition assay). She also showed acanthosis nigricans. The patient was diagnosed to suffer from a Type B insulin resistance syndrome. The patient's serum insulin and C-peptide levels were markedly elevated during hypoglycemia without insulinoma (2,313.8 microU/ml, 55 ng/ml, respectively). Interestingly, not only postprandial hyperglycemia but also fasting hypoglycemia was observed. Treatment with steroid pulse and subsequent high dose of prednisolone resulted in restoration of euglycemia associated with disappearance of insulin receptor antibodies and improvement of both serum hypocomplementemia and the high titer of ANA. Later, the patient's course was complicated by hemorrhagic shock due to duodenal ulcer and she died of subsequent pneumocystis carinii pneumonia. The presented patient developed a Type B insulin resistance syndrome induced by increased activity of SLE after she had been treated with hemodialysis for 5 years. This is the first reported case with such a history and constellation. It is recommended that SLE patients on dialysis are carefully followed-up by clinical and serological monitoring. Type B insulin resistance syndrome must be considered in the differential diagnosis of hypoglycemia in SLE patients on dialysis.

Observations on the occurrence of exacerbations in clinical course of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic disease that is characterized by an undulating course of exacerbations and remissions, and a major determinant of long-term prognosis is organ damage consequent to tissue injury that accompanies disease activity and toxicity of therapy. In this study, we evaluated which patients with SLE will develop an exacerbation and whether factors can be identified to predict the development of an exacerbation. Fifty-seven SLE patients (52 females) were included in this study. The exacerbation of SLE was found in 15 patients (26.3%). A relatively increased incidence of an exacerbation was found in younger SLE patients. An increased percentage of patients who had lupus nephritis at the time of diagnosis of SLE was found in patients with a subsequent exacerbation when compared with that in those without it. Increased incidence of an exacerbation was observed in patients who had decreased number of WBC and platelets, decreased level of C3 and CH50, and the presence positivity of anti-Sm antibodies at the time of the diagnosis. This study suggests that age, renal involvement, and the presence of decreased number of WBC and platelets, decreased level of complements anti-Sm antibodies are predictors of exacerbation.

Beneficial Effects of Complement Inhibition With Soluble Complement Receptor 1 (TP10) During Cardiac Surgery

TP10, a potent inhibitor of complement activation during cardiopulmonary bypass (CPB) has been shown to significantly reduce the incidence of death and myocardial infarction (MI) in high-risk male patients undergoing cardiac surgery. However, the effect of TP10 in females was undefined because of the limited number of females studied. To examine the possibility of a gender effect, this phase 2 multi-center trial was undertaken to determine whether TP10 would also limit ischemic damage in a larger sample size of high-risk females undergoing cardiac surgery on cardiopulmonary bypass (CPB). This prospective, double-blind, placebo-controlled, multi-center trial involved 297 high-risk (urgent surgery, CABG + Valve, reoperations, ejection fraction <30%) female patients randomized to receive a 5 mg/kg dose of TP10 (n=150) or placebo (n=147) as a 30-minute intravenous infusion before surgery. The primary end point was the incidence of death or MI at 28 days after surgery. Complement activation was assessed by levels of CH50 and SC5b-9 during and after CPB. TP10 was well tolerated and there were no differences in the safety profiles of the 2 groups. Although TP10 effectively suppressed complement activation (at 2 hours after CPB CH50 (mean+SD % change from baseline) 50+/-17% placebo versus 4+/-14% TP10; P=0.0001; SC5b-9 (ng/mL) 917+/-1067 placebo versus 204+/-79 TP10; P=0.0001), there was no difference in the primary end point between the groups (17% placebo versus 21% TP10; P=0.2550). The benefits of TP10 appear to be gender-related. and mechanisms other than complement activation may be responsible for myocardial injury in high-risk female patients during cardiac surgery on CPB.

Mizoribine therapy for patients with lupus nephritis: the association between peak mizoribine concentration and clinical efficacy

The clinical efficacy of mizoribine (MZR; 4-carbamoyl-1-b-D-ribofuranosylimidazolium) in patients with lupus nephritis was investigated. Thirteen Japanese patients with biopsy-proved lupus nephritis were enrolled in this study. A change in global assessments score, total protein (TP) of serum, serum creatinine, creatinine clearance (Ccr), proteinuria, titers of serum anti-ds DNA antibody, C3, C4, and hemolytic complement activity (CH50) were examined. Following MZR treatment, the level of urinary protein decreased (P < 0.05), whereas the level of Ccr increased (P < 0.05). Moreover, the level of TP significantly increased from 5.5 g/dl to 6.3 g/dl (P < 0.01) and the level of C3 increased significantly (P < 0.01). However, there was no change in the levels of both C4 and CH50. The titer of anti-ds DNA antibody significantly decreased (P < 0.05). The dosage of prednisolone could be tapered from 24.8 mg to 14.9 mg daily during the period. The clinical effects associated with MZR concentration in the blood revealed that there was a significant correlation between the peak MZR blood concentration of more than 0.66 microg/ml and clinical improvement (P = 0.021). Our results suggest that an optimal MZR blood concentration was important for the treatment of lupus nephritis.

Mizoribine therapy for patients with lupus nephritis: the association between peak mizoribine concentration and clinical efficacy

The clinical efficacy of mizoribine (MZR; 4-carbamoyl-1-b-d-ribofuranosylimidazolium) in patients with lupus nephritis was investigated. Thirteen Japanese patients with biopsy-proved lupus nephritis were enrolled in this study. A change in global assessments score, total protein (TP) of serum, serum creatinine, creatinine clearance (Ccr), proteinuria, titers of serum anti-ds DNA antibody, C3, C4, and hemolytic complement activity (CH50) were examined. Following MZR treatment, the level of urinary protein decreased (P < 0.05), whereas the level of Ccr increased (P < 0.05). Moreover, the level of TP significantly increased from 5.5 g/dl to 6.3 g/dl (P < 0.01) and the level of C3 increased significantly (P < 0.01). However, there was no change in the levels of both C4 and CH50. The titer of anti-ds DNA antibody significantly decreased (P < 0.05). The dosage of prednisolone could be tapered from 24.8 mg to 14.9 mg daily during the period. The clinical effects associated with MZR concentration in the blood revealed that there was a significant correlation between the peak MZR blood concentration of more than 0.66 µg/ml and clinical improvement (P = 0.021). Our results suggest that an optimal MZR blood concentration was important for the treatment of lupus nephritis.

Properdin deficiency in a boy with fulminant meningococcal septic shock

Bacterial meningitis is a rare presentation for congenital immunodeficiency, but meningococcal invasive diseases and meningitis have been associated with late complement component deficiencies and properdin deficiency. A 5-y-old boy of non-consanguineous parents was admitted to our hospital with meningococcal septic shock. He had previously been suffering from recurrent respiratory infections. His 13-y-old brother had also been treated for meningococcal meningitis when he was 7 y old. Immunological studies, done after recovery, on the patient and his two brothers revealed normal immunoglobulin, IgG subclasses, C3, C4 and CH50 levels. Haemolytic activity of the alternative complement pathway could not be detected, and properdin concentrations were <0.01 mg/l in serum samples from the patient and his brothers. The patient and family members received quadrivalent polysaccharide meningococcal vaccine. The patient was discharged on penicillin prophylaxis, and he remained healthy during the ensuing year. Our findings stress that measurement of the haemolytic activity of the alternative complement pathway in addition to classical pathway haemolytic complement activity should be performed in patients with meningococcal disease to reveal various forms of complement deficiency. This is particularly important when there is a family history, or recurrences or infection due to uncommon serogroups. Deficient individuals and affected family members might be protected from infection by vaccination.

Implication of B Lymphocytes in Endotoxin-Induced Hepatic Injury After Partial Hepatectomy in Rats

Lymphocyte population constitutes major defense mechanism against endotoxemia, but the role of B lymphocytes in endotoxin-induced hepatic injury after hepatectomy is not clear. We used lymphopenic (L(-)) rats by single administration of anti-rat lymphocyte serum, nu/nu athymic (T(-)) rats, B cell-ablated (B(-))rats by intermittent injection of anti-immunoglobulin (Ig) micro-chain from birth, and their vehicle controls. These animals were subjected to two-thirds hepatectomy with subsequent intravenous lipopolysaccharides (LPS, 1.5 mg/kg) administration. The survival rate, plasma alanine transaminase (ALT), tumor necrosis factor-alpha (TNF-alpha) and IgM levels, and total hemolytic activity (CH50) were determined. Hepatic tissue deposition of IgM or C3 was assessed with immunohistochemistry. The 24-h survival rate in control animals was 20%, whereas those in L(-), T(-), and B (-) animals were 80, 0, and 100%, respectively. Lymphocyte-sufficient control (L(+)) and B cell-sufficient control (B(+)) animals showed a rapid elevation of plasma TNF-alpha levels 1 h after the challenge, followed by an increase in plasma ALT levels. In B(+) group, plasma IgM levels were increased and CH50 activities were decreased 4 h after LPS injection with significant difference compared to those at time 0. Liver histology showed massive hepatic necrosis with a dense accumulation of IgM and C3 deposits 4 h after LPS administration. B cell ablation significantly ameliorated plasma ALT, IgM, and CH50 levels, showing less histological liver damage. B lymphocytes susceptible to LPS might be implicated in the development of endotoxin-induced hepatic injury after partial hepatectomy.

The effect of moderate‐dose corticosteroids in preventing severe flares in patients with serologically active, but clinically stable, systemic lupus erythematosus: Findings of a prospective, randomized, double‐blind, placebo‐controlled trial

Serial measurements of anti-double-stranded DNA (anti-dsDNA) and complement are routine in the management of systemic lupus erythematosus (SLE), but their utility as biomarkers in preemptive treatment to prevent flares remains a subject of controversy. We hypothesized that concomitant elevation of anti-dsDNA and C3a can predict SLE activity in patients with stable or inactive disease and that short-term treatment with corticosteroids can avert flares. In this prospective, randomized, double-blind, placebo-controlled trial, 154 patients were evaluated monthly for up to 18 months, with measurements of C3a, C3, C4, CH50, and anti-dsDNA levels. Patients who remained clinically stable but showed serologic evidence of an SLE flare (elevation of both the anti-dsDNA level by 25% and the C3a level by 50% over the previous 1-2 monthly visits) were randomized to receive either prednisone or placebo therapy at a dosage of 30 mg/day for 2 weeks, 20 mg/day for 1 week, and 10 mg/day for 1 week. Forty-one patients (21 randomized to prednisone and 20 randomized to placebo) experienced a serologic flare. Analysis of severe flares occurring <or=90 days from randomization revealed that 6 occurred in patients taking placebo and none occurred in patients taking prednisone (P = 0.007). Severe flares resulted in an increase in the prednisone dosage to >40 mg/day and/or the addition of an immunosuppressive agent. Furthermore, improvement in scores on the Systemic Lupus Erythematosus Disease Activity Index, decreased levels of anti-dsDNA antibodies, and increased levels of C4 occurred 1 month after initiation of prednisone treatment. These preliminary data support our hypothesis that in a subset of clinically stable SLE patients with a combination of elevated C3a and anti-dsDNA levels, short-term corticosteroid therapy may avert a severe flare.

Which complement assays and typings are necessary for the diagnosis of complement deficiency in patients with lupus erythematosus? A study of 25 patients

Introduction: Deficiencies in components of the classical pathway of complement activation are strong risk factors for lupus erythematosus (LE).Yet, it has not been addressed whether the conventional measurements of the serum hemolytic CH50 activity and antigenic concentrations of C3 and C4 are sufficient to asses a deficiency in C4A, C4B or C2 components, the most common deficiencies associated with LE. Patients and methods: In a retrospective series, we performed complement analyses in 35 patients with LE who were systematically screened for a complement deficiency. The majority of patients had cutaneous LE with mild systemic involvement and no complement consumption. Of 25 patients (72%) with complement deficiency we found 13 with a partial C4A deficiency, 2 with a complete C4A deficiency, 6 with a partial C4B deficiency, 2 with a complete C4B deficiency and 2 with a combined partial C2 and C4A deficiency. Results: The total complement activity (CH50) was decreased in only one out of two patients with complete C4B deficiency. CH50 level was found to be low–normal (35–38 U/ml − 1 ) in one patient with partial C4B deficiency, one patient with complete C4B deficiency and both patients with combined partial C4A and C2 deficiency. Total C4 levels were normal in 9 out of 13 the patients with a partial C4A deficiency and in 2 out of 6 patients with a complete C4B deficiency. The antigenic concentration of C3 was low in only 1 patients with a complete C4B deficiency and within the normal range in all the others patients. Overall, 50% of the patients had normal or elevated C3, C4, and CH50 levels. Discussion: This study emphasizes that the usual measurements of CH50, C3 and C4 levels are not adequate to detect a C4 and/or C2 deficiency in patients with LE. In epidemiologic or investigative studies addressing the prevalence of complement deficiency, more elaborated diagnostic tests, such as C4 protein allotyping, C2 level measurement and genetic screening for type I C2 deficiency should also be performed.

Infections in systemic lupus erythematosus: a prospective and controlled study of 110 patients

We decided to analyse the incidence and characteristics of infection in systemic lupus erythematosus (SLE) and determine the related risks factors. One-hundred and ten SLE patients and 220 controls were prospectively followed up over three years and all the infectious episodes were recorded. A case-control design was established to identify risk factors of infection. Thirty-nine SLE patients suffered at least one infection (36%) versus 53 controls (22%), RR = 1.63 (P < 0.05). The incidence of urinary infections, pneumonia and bacteraemia without known focus was significantly greater in SLE. E. coli was the chief isolated microorganism (21.3%). In the univariate analysis, nephritis, SLE activity, leucopenia, anti-dsDNA levels above 20 IU/mL, CH50 levels under 300 IU/mL, ever use of steroids, daily dose of prednisone higher than 10 mg and ever use of cyclophosphamide were significantly associated with infection. In the multivariate analysis, total serum complement levels below 300 UU/mL and a daily dose of prednisone above 20 mg during at least one month plus ever use of cyclophosphamide were found to be significant (P < 0.0001). We conclude that patients with SLE have an increased overall risk for infection and they are especially prone to develop urinary infection, pneumonia and bacteraemia without focus. Hypocomplementaemia represents an independent predictive factor for infection. It seems mandatory to closely follow up SLE patients with low complement levels and instruct them to report any suspicious sign of infection, especially in those receiving more than 20 mg/day of prednisone who have also been administered cyclophosphamide.

Cutaneous Lesions in a Patient With Chronic Hepatitis C Virus

A 66-year-old man presented with skin lesions that had developed 4 days previously. He had a history of membranoproliferative glomerulonephritis and chronic hepatitis virus infection, but he refused treatment. Physical examination revealed cutaneous lesions (Figure A). Cryoglobulins were present. His serum C3 level was normal and his CH50 and C4 levels were decreased. An increase of polyclonal immunoglobulin G was present. A skin biopsy examination showed leukocytoclastic vasculitis. The patient refused hepatitis treatment and a prednisone treatment was started. After a 6-month follow-up evaluation, the patient had no evidence of cutaneous vasculitis and he receives no steroids. The etiopathogenesis of leukocytoclastic vasculitis is not very well known.1Albrecht Schirren C. Zachoval R. Shirren C.G. et al.A role for chronic hepatitis C virus infection in a patient with cutaneous vasculitis, cryoglobulinemia, and chronic liver disease.Dig Dis Sci. 1995; 40: 1221-1225Crossref PubMed Scopus (31) Google Scholar, 2Hamid S. Ponciano D.C. Lee M.L. Urticarial vasculitis caused by hepatitis C virus infection: response to interferon alfa therapy.J Am Acad Derm. 1998; 39: 278-280Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar Some investigators think that leukocytoclastic vasculitis is caused by deposition of immune complexes in postcapillary venules, probably cryoglobulins that destroy the vessel’s wall.2Hamid S. Ponciano D.C. Lee M.L. Urticarial vasculitis caused by hepatitis C virus infection: response to interferon alfa therapy.J Am Acad Derm. 1998; 39: 278-280Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar However, other investigators have shown that hepatitis C virus is present in the vessel walls.3Durand J.M. Kaplanski G. Richard M.A. et al.Cutaneous vasculitis in patient infected with hepatitis C virus Detection of hepatitis C virus RNA in the skin by polymerase chain reaction.Br J Dermatol. 1993; 128: 359-360Crossref PubMed Scopus (36) Google Scholar In this case, we think that leukocytoclastic vasculitis probably was produced by immune complexes and not by hepatitis C virus.

Acute Renal Failure due to IgM-λ Glomerular Thrombi and MPGN-Like Lesions in a Patient With Angioimmunoblastic T-Cell Lymphoma

A 70-year-old man with angioimmunoblastic T-cell lymphoma developed acute renal failure. Laboratory data showed decreased levels of serum C3, C4, and CH50, elevated immunoglobulin M (IgM) levels, and the presence of cryoglobulinemia (IgM-lambda). Renal biopsy showed membranoproliferative glomerulonephritis-like lesions with azan-red-stained thrombi in the glomerular capillary lumen. Immunofluorescence showed that IgM-lambda stained strongly in the glomerular capillary lumen, equal to the azan-red-stained thrombi, whereas C3 and C4 staining was negative. Electron microscopy showed electron-dense deposits in the subendothelial space and glomerular thrombi lacking fine fibrillar structure. These findings suggest that cryoglobulin, which consists of monoclonal IgM-lambda, induced glomerular thrombi and acute renal failure in a patient with angioimmunoblastic T-cell lymphoma.

Complement as a predictor of further miscarriage in couples with recurrent miscarriages

The clinical significance of complement is unclear in patients with unexplained recurrent miscarriage, though low levels of complement 3 (C3) and/or complement 4 (C4) are reported to be associated with the antiphospholipid syndrome (aPS). We therefore investigated whether C3 and C4 have a predictive value for subsequent miscarriages. In total, 215 patients with a history of two consecutive first-trimester miscarriages and no abnormal chromosomes in either partner, no uterine anomalies and no antiphospholipid (aPL) antibodies were examined. Blood tests for C3, C4, total haemolytic complement (CH50), immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM) were performed before subsequent pregnancy. Patients were then followed up without treatment, and their pregnancy outcomes were compared with their previous blood test results. From 215 pregnant patients, 45 subsequently miscarried, whereas the remainder had a live birth. There was no relation with serum CH50, IgG, IgA and IgM levels, but C3 and C4 levels in patients with subsequent miscarriage were significantly higher than in those whose pregnancy was successful. In patients with two previous miscarriages, C3 and C4 levels were higher in those women who had a third miscarriage, than in women that went on to have a live birth.

Changes of complement in recurrent abortion and pregnancy loss with antiphospholipid antibody positive

In order to know the comlement activation, the changes of compliment were evaluated in recurrent abortion and pregnancy loss patients with antiphospholipid antibody (APA) positive. Serum samples were taken from 82 patients with more than 2 recurrent abortion patients and/or pregnancy loss. Fifty eight cases of 82 patients were APA and antinuclear antibody negative without autoimmune disease. Anticardiolipin antibody (ACA), anti CL/beta2-GPI antibody (CL/beta2-GPI) were measured using ELISA. Lupus anticoagulant (LAC) was measured using diluted RVVT. CH50 and C3 and C4 were measured as complements. The number of positive cases of ACA, CL/beta2-GPI, LAC was 23, 9 and 5 cases, respectively. The levels (mean+/-SD) of CH50, C3 and C4 in ACA positive and negative cases were 38.8+/-8.3 U/ml, 82.7+/-20.1 mg/dl, 18.5+/-5.7 mg/dl and 42.4+/-6.9 U/ml, 93.5+/-17.6 mg/dl, 21.1+/-4.6 mg/dl, respectively. The levels of CH50, C3 and C4 in positive cases were significantly lower than negatives. The levels of CH50, C3 and C4 in CL/beta2-GPI and LAC positive cases were also significantly lower than negatives. The comlement activation was demonstrated in recurrent abortion and pregnancy loss with antiphospholipid antibody positive.

Immunological Characteristics of Hatano High-and Low-Avoidance Rats

Hatano high- and low-avoidance (HAA and LAA) rats have been genetically selected on the basis of their two-way active avoidance behavior, and have been shown to differ in other behavioral and hormonal parameters. Since close interconnections among the nervous, endocrine and immune systems have been well documented, these two strains might possess differences in aspects of immunological action. In Experiment 1, plasma levels of IgG, IgM, complement 3 (C3), classical pathway hemolytic complement (CH50) and beta(2)-microglobulin were compared between males of the two strains at 5 and 24 weeks of age. Plasma levels of IgG and CH50 were lower in LAA than HAA rats at 5 weeks of age, whereas those differences disappeared at 24 weeks of age. There were no differences between the two strains in plasma levels of IgM, C3 and beta(2)-microglobulin. In Experiment 2, antibody production to sheep red blood cells (SRBC) and mitogen-induced lymphocyte proliferation were compared between 12-week-old males of the two strains. Antibody responses in the PFC assay, plasma anti-SRBC-IgM levels and spleen weights were higher in LAA than HAA rats. LPS-induced lymphocyte proliferation was greater in LAA than HAA rats. It was concluded that HAA rats show earlier development of immunological development, but that antibody production and mitotic response of B lymphocytes may be more pronounced in adult LAA than HAA rats. The strain differences observed in the immunological response may indicate the usefulness of using Hatano rats in studies of behavioral-immunological relationships.

Tumor Burden Related Immunodeficiency in Lymphoma Patients and Clinical Course.

The association of lymphoma with a plethora of secondary immune defects is well established. However, most investigations were performed many years ago and little is known about disease specific alterations of the immune system. From January 2003 to August 2004 50 patients with newly diagnosed malignant lymphoma were analyzed and compared with 50 healthy volunteers Corresponding in age and gender. Parameters of cellular and humoral immunity, including CBC, FACS analysis of lymphocyte subpopulations, cytokines (sIL2-R, IL-6, IL-10, TNF-a), serum complement components C3c, C4, CH50 and total concentrations of serum immunoglobulin IgG, IgM, IgA were measured. The median number of CD3+ and CD4+ lymphocyte subsets (p≤0.01) were significantly lower in lymphoma patients compared with matched healthy volunteers. The number of CD8+ T-cells was decreased in patients with bulky disease (p≤0.01). High-intermediate/high risk lymphoma (IPI 3-4 or aaIPI 2-3) had significantly higher CH50 (p=0,02), C3c (p≤0,01), sIL2-R (p≤0,01) and TNF-a levels (p=0,05) than patients with low/low-intermediate risk lymphoma. Infectious complications after chemotherapy (n=14) occurred frequently in patients with high initial LDH (p=0,04), low number of CD4+ (p=0,02) or CD8+ T-cells (p=0,04) and high levels of sIL2-R (p=0,02) or TNF-a (p=0,03). Relapse (n=6) was also observed in patients with decreased CD8+ T-cells (p=0,04) and in patients with high C4 levels (p=0,02). These results indicate that tumor burden in lymphoma patients significantly influenced the number of lymphocyte subsets, serum cytokine levels (sIL2R, TNF- a) and complement components (CH50, C3c). IPI-score and clinical course (infections and relapse) were related to the immunodeficiency. We conclude that measurement of peripheral blood lymphocyte subsets, cytokines and complement factors can be expected to improve existing methods of risk assignment in lymphoma.

Massive mesenteric edema in a patient with type I hereditary angioedema

We report a patient with hereditary angioedema (HAE) presenting with skin edema and abdominal pain. Laboratory examination showed reduced levels of CH50, C2, C4, and C1 inhibitor (C1-INH). Abdominal computed tomography (CT) showed marked mesenteric edema and wall thickening of the duodenum and transverse colon. Acute abdominal pain is common in HAE and is difficult to distinguish from surgical emergency. Massive mesenteric edema on CT is a rare, but specific, sign suggesting HAE.

Characteristics of acute glomerulonephritis associated with human parvovirus B19 infection

Acute glomerulonephritis (AGN) is a rare complication of human parvovirus B19 (HPB19) infection. The clinical and pathological features of AGN associated with HPB19 (HPBAGN) have not yet been fully elucidated. We analyzed 10 HPBAGN cases, focusing on their clinical and serological features. We also performed histopathological examinations of renal biopsy specimens obtained from three of the 10 patients on day 15, 19 and 23, respectively, after the onset of symptoms. The phenotype of the glomerular infiltrating leukocytes in HPBAGN was determined by immunohistochemical staining and compared with that of glomerular infiltrating leukocytes in poststreptococcal AGN (PSAGN) and lupus nephritis. The clinical course and laboratory data of the HPBAGN patients revealed female preponderance (male = 0, female = 10), erythema in 9 of the 10 patients, leukopenia in 3, positive antinuclear antibody titer in 4, hypocomplementemia with low levels of C3, C4, and CH50 in 9, and liver dysfunction in 7. Endocapillary hypercellularity of leukocytes was demonstrated in all three patients who underwent renal biopsy. In comparison with PSAGN and lupus nephritis with crescents there were less neutrophil in HPBAGN compared to marked macrophage infiltrates that were equally intense in both the control and the HPBAGN group. Our findings indicate that HPBAGN is characterized by female preponderance, erythema, leukopenia, positive antinuclear antibody titer, and hypocomplementemia, and that minor neutrophil infiltration may be related to mild clinical manifestations despite the marked fixation of glomerular leukocytes in HPBAGN.

Frequency in Spanish Population of Familial Complement Factor 2 Type I Deficits and Associated HLA Haplotypes

We present two familial cases of complement factor 2 (C2) type I deficiency. Probands had experienced severe pyogenic bacteria infections in childhood and had undetectable levels of C2 and very low level of CH50. Both children were homozygous for the deletion of 28 bp in exon 6 of the C2 gene. Human leukocyte antigen (HLA) typing in family 1 had the commonly reported associations, but family 2 demonstrated a new association of the mutated C2 gene to HLA-A*3101, -Cw*0602, -B*1801, and -DRB1*0901. In addition, for the first time, the frequency of the 28-bp deletion of C2 and its HLA haplotypic associations have been analyzed in a sample of the Spanish population containing 790 haplotypes and 105 phenotypes. Cw*0602 is frequently found in Spanish haplotypes linked to the C2 mutated gene instead of the commonly reported -Cw*1203. The presence of heterozygous or homozygous individuals for the C2 deletion with low levels of IgD in both families supports the existence of a putative dominant susceptibility gene for IgD deficiency in haplotype HLA-B18, -S042, and -DR2. The frequency of the C2 28-bp deletion in heterozygosis is 1.4% (gene frequency 0.007) in Spanish healthy controls, similar to that reported in other white populations.

The research on the relationship between the polymorphism of 1082A/G, anti-inflammatory interleukin-10 gene promoter with its effect of preventing ESRD patients from microinflammation and arteriosclerosis

We do this investigation in order to reveal the relationship between the polymorphism of 1082A/G, anti-inflammatory interleukin-10 gene promoter, and end stage renal disease (ESRD) patients microinflammatory state and arteriosclerosis (AS). We used PCR-RFLP to measure the various kinds of distribution of IL-10 gene-1082A/G genotype and relevant indexes of microinflammatory state and AS of 870 ESRD patients and 1000 healthy persons of control group and to analyze the mechanism of its protection effect keeping ESRD patients away from microinflammation and arteriosclerosis. Compared with the control group, CRP, TNF-alpha, CH50, C3, IL-10 and Alb of ESRD group were in the normal range, but still significantly higher than those of the control group, while IL-10, Alb were significant lower (P < 0.05). The genotype distribution and allele frequency of IL-10A/G gene had no significant differences between the healthy group and the control group (P > 0.05). Levels of CRP, TNF-alpha, CH50 and C3 of ESRD patients with IL-10A/A genotype were significantly higher than those of ESRD patients with G/G and G/A genotype (P < 0.05), while IL-10 and Alb were significantly lower (P < 0.01). The production of IL-10 in serum from patients with IL-10A/A genotype was significantly lower than that of patients with G/G and G/A genotype (P < 0.01). The incidence rate of AS of patients with IL-10-1082A/A genotype was significantly higher than that of patients with G/G and G/A genotype (P < 0.01). The raise of AS incidence rate was correspondent with the decline of serum IL-10 and raise of serum CRP and Fib. The IL-10A/A genotype is a predictable factor of microinflammatory state and high AS incidence rate in ESRD patients. We use IL-10G/G genotype to modulate the high production of serum IL-10, to decline inflammatory reaction and to keep away from microinflammation and AS in ESRD patients. We should work hard on improving the dialysis membrane to reduce the anti-inflammatory factors in uremia for chronic renal failure patients with high arteriosclerosis risk.