Low-dose Intravenous Immunoglobulin Research Articles

Can low-dose intravenous immunoglobulin be an alternative to high-dose intravenous immunoglobulin in the treatment of children with newly diagnosed immune thrombocytopenia: a systematic review and meta-analysis

Intravenous immunoglobulin (IVIg) is a first-line treatment for children with newly diagnosed immune thrombocytopenia (ITP). Higher doses of IVIg are associated with a more insupportable financial burden to pediatric patients’ families and may produce more adverse reactions. Whether low-dose IVIg (LD-IVIg) can replace high-dose IVIg (HD-IVIg) has yet to be established. We conducted a comprehensive literature search from the establishment of the database to May 1, 2023, and eventually included 22 RCTs and 3 cohort studies compared different dosages of IVIg. A total of 1989 patients were included, with 991 patients in the LD-IVIg group and 998 patients in the HD-IVIg group. Our results showed no significant differences between the two groups in the effective rate (LD-IVIg: 91% vs. HD-IVIg: 93%; RR: 0.99; 95%CI: 0.96–1.02) and the durable remission rate (LD-IVIg: 65% vs. HD-IVIg: 67%; RR: 0.97; 95%CI: 0.89–1.07). Similar results were also found in the time of platelet counts (PC) starting to rise (MD: 0.01, 95%CI: -0.06–0.09), rising to normal (MD: 0.16, 95%CI: -0.03–0.35), and achieving hemostasis (MD: 0.11, 95%CI: -0.02–0.23) between the two groups. Subgroup analysis showed the effective rate of 0.6 g/kg was equal to 1 g/kg subgroup (91%) but higher than 0.8 g/kg subgroup (82%), and a combination with glucocorticoid may contribute to effect enhancement (combined with glucocorticoid: 91% vs. IVIg alone: 86%) whether combined with dexamethasone (92%) or methylprednisolone (91%). Besides, the incidence rate of adverse reactions in the LD-IVIg group (3%) was significantly lower than the HD-IVIg group (6%) (RR: 0.61; 95%CI: 0.38–0.98). So low-dose IVIg (≤ 1 g/kg) is effective, safe, and economical, which can replace high-dose IVIg (2 g/kg) as an initial treatment. This systematic review was registered in PROSPERO (CRD42022384604).

The Combination of Intravenous Immunoglobulin (IVIG) and Low Does Recombinant Human Thrombopoietin (rhTPO) for the Management of Corticosteroid/IVIG Monotherapy-Resistant Immune Thrombocytopenia in Pregnancy

Introduction Primary immune thrombocytopenia (ITP) is a common autoimmune disease characterized by a low platelet count resulting from antibody-mediated platelet destruction and insufficient platelet production. ITP, with a prevalence of 1 in 1000-10 000 pregnancies, accounts for approximately 3% of all causes of thrombocytopenia in pregnancy and is reported to be the most common cause of thrombocytopenia in the first and early second trimesters. It has been revealed that severe ITP is associated with devastating outcomes. It remains a challenge to manage pregnant patients with ITP. First-line treatment options in pregnant ITP patients currently include corticosteroids and intravenous immunoglobulin (IVIg). However, previous studies reported that the response rate of pregnant ITP patients to corticosteroids was less than 40% and that to IVIg was 38-56%, which was lower than that of nonpregnant ITP patients. The second-line treatment options are limited for pregnant ITP patients. Recombinant human thrombopoietin (rhTPO), a full-length and glycosylated TPO with a molecular weight of 90 000 Daltons developed by 3SBIO (Shenyang, China), has also been approved by the China State Food and Drug Administration as a second-line option for nonpregnant ITP patients. It cannot cross the placenta theoretically with such a large molecular weight, and thus, it has an apparent theoretical advantage over the two TPO mimetics since it would not impact the fetus. A study investigating the application of rhTPO in pregnancy suggested that rhTPO was a potentially effective and well-tolerated treatment option for ITP patients during pregnancy. It might be explained that the development of ITP was associated with increased platelet destruction and impaired platelet production, and the combination of IVIg and TPO mimetics impacts these two targets since IVIg could reduce platelet destruction, whereas TPO mimetics could increase platelet production. Therefore, we conducted a monocenter, single-arm, open-label study to investigate the efficacy and safety of low-dose rhTPO plus IVIg in pregnant corticosteroid/IVIg monotherapy-resistant ITP patients. Methods This study was registered at www.clinicaltrials.gov as NCT05634824.The following criteria were considered: patients have a diagnosis of primary ITP before or first onset during pregnancy; patients ≥ 18 years; patients complicated with bleeding manifestations and/or have a platelet count < 30 × 10^9/L and failed to respond to initial treatment of corticosteroids or intravenous immunoglobulin (IVIg) monotherapy or relapsed during the tapering or discontinuation of corticosteroids. For those patients, the initial combination therapy consisted of rhTPO at an initial dose of 150 U/kg once daily subcutaneously for 28 days and IVIg 400 mg/kg per day for 5 days. If the platelet count was in the range of 30 to 50 × 10^9/L, the combination therapy was repeated. To reduce the risk for thrombocytosis, patients received maintenance therapy consisting of rhTPO at a dose of 150 U/kg per day if the platelet count rose above 50 × 10^9/L, and treatment was discontinued when platelet counts exceeded 100 × 10^9/L. After delivery, the treatment consisted of rhTPO 150 U/kg per day, and the dose was maintained if the platelet count exceeded 30 × 10^9/L. In addition, IVIg 400 mg/kg per day for 5 days was added if the platelet count could not be maintained above 30 × 10^9/L. If patients did not achieve a count of 30 × 10^9/L within 4 weeks, treatment was also discontinued. Results The study included 19 patients with thrombocytopenia during pregnancy who were admitted to Peking University People's Hospital from December 1, 2022, to May 30, 2023, all of whom had failed hormone and IVIG treatment. The median age of those patients was 34 years old (range 20 to 42 years old), and the median platelet count before treatment was 13×10^9/L (range 1-30×10^9/L). The four-week response rate was 63.2% (12/19), and the median response time was 7.5 days (range 5 to 35 days). There were no treatment-related adverse reactions. Conclusions Low-dose rhTPO plus IVIg in pregnant corticosteroid/IVIg monotherapy-resistant ITP patients is effective and safe. These findings suggest that IVIg plus low-dose rhTPO may represent a potential combination therapy for pregnant patients with ITP.

Parvovirus B19 infection after kidney transplantation: A single centre experience

BackgroundParvovirus B19 is an uncommon cause of anaemia in kidney transplant recipients (KTRs). The study aims to determine the incidence, clinical presentation, laboratory findings and outcome of parvovirus B19-related anaemia in KTR. MethodWe conducted a 12-year retrospective, single-centre study describing the clinical profile of KTRs with parvovirus B19-related anaemia. ResultAmongst the 714 patients who underwent kidney transplantation between January 2011 and January 2023, (cumulative follow-up: 1287 patient-years), six females and one male, developed parvovirus B19-related anaemia. The incidence proportion (risk) is 0.98% with an incidence rate of 5.43 cases per 1000 patient-year. The median duration from transplant to development of anaemia was 6 weeks (range: 4–40 weeks). The mean fall in haemoglobin was 2.88 ± 1.55 gm/dl; concomitant leukopenia and thrombocytopenia were observed in 57.1 and 28.6% of patients. Three patients responded to a reduction in immunosuppression, the four non-responders required the administration of low-dose intravenous immunoglobulin. The mean duration from initiation of therapy to a sustained rise in haemoglobin was 7.71 ± 2.62 weeks. None of the patients had a relapse of the infection. ConclusionsParvovirus B19 infection is an uncommon cause of post-transplant refractory anaemia. The key to successfully managing such patients includes a high index of suspicion, early diagnosis and reduction of immunosuppression with or without administration of intravenous immunoglobulin.

Low-dose intravenous immunoglobulin for children with newly diagnosed immune thrombocytopenia: protocol of a systematic review and meta-analysis

IntroductionIntravenous immunoglobulin (IVIg) is a first-line treatment for children with newly diagnosed immune thrombocytopenia (ITP). However, the cost of IVIg is high. Higher doses of IVIg are associated with a...

Successful Pregnancy and Delivery at Term Following Intravenous Immunoglobulin Therapy with Heparin for Unexplained Recurrent Pregnancy Loss Suspected of Immunological Abnormalities: A Case Report and Brief Literature Review

About 60% of cases of recurrent pregnancy loss have unexplained etiology. Immunotherapy for unexplained recurrent pregnancy loss is still unestablished. A 36-year-old woman, not obese, had a stillbirth at 22 gestational weeks and a spontaneous abortion at 8 weeks. She had been examined for recurrent pregnancy loss at previous clinics with no significant findings. When she visited our clinic, a hematologic test showed a Th1/Th2 ratio imbalance. Ultrasonography, hysteroscopy, and semen analysis showed no abnormalities. She successfully conceived by embryo transfer in hormone replacement therapy cycle. However, she had a miscarriage at 19 weeks. The baby had no deformities, but a chromosomal test was not performed, according to the parents' will. The placenta pathologically suggested hemoperfusion problems. Her and her husband's chromosomal tests showed normal karyotypes. Other examinations revealed a repeated Th1/Th2 ratio imbalance and a high resistance index of uterine radial artery blood flow. She was administered low-dose aspirin, intravenous immunoglobulin, and unfractionated heparin after the second embryo was transferred. Her baby was healthily born by cesarean section at 40 weeks. Intravenous immunoglobulin therapy can be a choice for recurrent miscarriage without risk factors because it has clinically beneficial influences on the patient's immunological aberration.

Role of therapeutic plasma exchange as a desensitization therapy in human leukocyte antigen incompatible renal transplant patients: A single-center experience

ObjectiveDespite an increase in the rate of successful live donor renal transplantation done annually, the number of potential recipients with acceptable donors is relegated to the ever-expanding cadaver-donor waiting list due to sensitization to human leukocyte antigen (HLA) antibodies. If not sufficiently suppressed, these preformed HLA antibodies can trigger antimicrobial resistance (AMR) and early graft loss. To ameliorate this situation, various desensitization treatments are administered to provide a survival benefit to highly sensitized patients. MethodOne hundred and six patients in the time frame of January 2017 to March 2019 were included in the study group. The desensitization protocol included therapeutic plasma exchange and administration of low-dose intravenous immunoglobulin (100 mg/kg per therapeutic plasma exchange (TPE) session) to highly sensitized patients (treatment group) who subsequently underwent renal transplantation after negative pre-transplant Centers for Disease Control and Prevention Luminex crossmatch (CDC/LumXM). We compared graft survival rates between the group undergoing desensitization (treatment group) and matched control group of patients that underwent HLA-compatible transplantation. ResultsIn the treatment group, Kaplan-Meier analysis estimates an average rate of patient graft survival of 95.2% at 3 years post-transplant, as compared with the rate of 86.9% in the same time frame for the control-matched group (p < 0.05 for both comparisons). ConclusionDesensitization treatment with TPE before live donor renal transplantation in the case of patients with HLA sensitization provides better survival benefits along with monitoring for donor-specific antibodies (DSAs) and other infections, rather than waiting for a compatible organ donor. The data lays out evidence that desensitization treatments can assist overcome HLA incompatibility barriers in live donor renal transplantation.

Primary antibody deficiencies represent an underestimated comorbidity in asthma patients: efficacy of immunoglobulin replacement therapy in asthma control

Objective Primary antibody deficiencies (PAD) are an underestimated comorbidity in asthma and its treatment could improve disease control. Methods a retrospective cohort of asthmatics, affected by IgG subclass deficiency or unclassified antibody deficiency and treated with low-dose intravenous immunoglobulin replacement therapy (IRT) was recruited. Demographic and clinical data, chest CT scan, blood eosinophils, atopy, chronic oral corticosteroid (OCS) therapy were evaluated at baseline. Asthma exacerbations, lower respiratory tract infections (LRTI), upper respiratory tract infections (URTI) and asthma-related hospitalizations were assessed after one and two years of IRT. Results 57 moderate-to-severe asthmatics were enrolled, mostly affected by T2 low asthma (39/57, 68.4%). After one year, IRT was effective in improving, irrespective of bronchiectasis, atopy, eosinophils and PAD type: 1) trough IgG (826.9 ± 221.3 vs 942.2 ± 195.1 mg/dl; p < 0.0001) and IgG subclasses (IgG1 355.4 ± 88.4 vs 466.7 ± 122.3, p < 0.0001; IgG2 300.1 ± 130.1 vs 347.6 ± 117.3, p < 0.0005) serum levels. 2) asthma exacerbations (6.4 ± 4.1 vs 2.4 ± 1.9, p < 0.0001), LRTI (4.3 ± 3.9 vs 1.3 ± 1.5, p < 0.0001) and hospitalization rate (0.26 ± 0.7 vs 0.05 ± 0.2, p < 0.01). These results persisted after 2 years of therapy. Estimated mean cumulative OCS exposure was reduced by 4500 mg over the 2-year period. Conclusions low-dose IRT is effective in improving asthma control and lessening OCS burden in asthmatics affected by PAD.

Effects of low-dose intravenous immunoglobulin as the adjunctive therapy in septic shock patients with and without hypogammaglobulinemia: a retrospective cohort study

Intravenous immunoglobulin (IVIG) therapy has a reported adjunctive effect in the treatment of sepsis, but in light of results from a large-scale randomized control trial (RCT), evidence for improved prognosis with IVIG therapy is currently deemed insufficient. In recent years, there have been many reports of low serum immunoglobulin G (IgG) as a poor prognostic factor in septic patients. Under Japan's national health insurance system, IVIG is administered for severe infections at a dose of 5 g/day for three days (total 15 g or 0.3 g/kg). At present, IVIG administration is not specifically formulated for septic patients with hypogammaglobulinemia. It is clinically significant to investigate whether serum IgG levels can serve as a biomarker to predict the efficacy of IVIG treatment for septic shock and help to identify those patients who might benefit from an adjunctive IVIG treatment. The purpose of this study was to compare the efficacy of this low-dose IVIG as an adjunctive therapy in septic shock patients with and without hypogammaglobulinemia. In this retrospective cohort study, patients who received low-dose IVIG (5 g/day for 3 days) as adjuvant therapy for septic shock were enrolled. These patients were divided into two groups based on a median serum IgG level of 829 mg/dL (<830 mg/dL defined as hypogammaglobulinemia) prior to IVIG administration. To assess the efficacy of low-dose IVIG administration (0.3 g/kg), 28-day survival probability as the primary outcome, and the lengths of artificial ventilation and intensive care unit (ICU) stays as the secondary outcomes were compared using the Kaplan-Meier method, the log-rank test, the Wilcoxon or Mann-Whitney U test. A total of 80 patients with septic shock that underwent IVIG treatment in the ICU were enrolled. These patients were divided into two groups based on a median serum IgG level. Survival probabilities at 28 days were 90.0% and 85.0% in the high- and low-level groups, respectively, and there was no significant difference between the two groups (P=0.457). There are not also significant differences in median lengths of artificial ventilation (6 vs. 9 days, P=0.215) and ICU stays (10 vs. 12 days, P=0.199) after IVIG administration. Logistic regression revealed that these clinical outcomes were not associated with serum IgG after adjusting for confounding factors as the antibiotics. Serum IgG levels was not associated with the clinical outcomes by low-dose IVIG treatment. Our results suggest that the prognosis of low-dose IVIG as adjunctive therapy in patients with septic shock might be no different with and without hypogammaglobulinemia.

Renal infarction associated with low dose intravenous immunoglobulin in a kidney transplant recipient with sepsis: a case report and literature review

BackgroundThe use of human intravenous immunoglobulin gamma (IVIG) is associated with thromboembolic events as a complication. There are few reported cases of renal infarction during IVIG use in the general population, but transplant kidney may be more susceptible to thromboembolic events following IVIG use.Case presentationA 41-year-old woman visited with fever and pain at the transplant kidney. Six years ago, she underwent kidney transplantation from a deceased donor. Laboratory and radiologic findings were compatible to septic condition, secondary to acute pyelonephritis. We started antibiotics, inotropics, and IVIG. The patient abruptly developed gross hematuria and urine output decreased to 100 cc/day during IVIG administration. Renal doppler and pathologic findings revealed renal infarction. Oliguria and azotemia persisted and she is undergoing maintenance hemodialysis.ConclusionOur case shows that infarction of transplant kidney can be caused by IVIG use in a patient with severe infection. Thus, when using IVIG for kidney transplant patients with high risk of thromboembolic events, we may be careful to prevent the thromboembolic events.

ABO-Incompatible Living Donor Liver Transplantation With a Simplified Desensitization and Immunosuppression Protocol: A Single-Center Retrospective Study.

New desensitization strategies have made ABO-incompatible living donor liver transplant an attractive option for patients with end-stage liver disease. We aimed to report our experience with 20 consecutive patients who underwent ABO-incompatible living donor liver transplant using a simplified desensitization and immunosuppression regimen. We retrospectively analyzed 20 ABO-incompatible living donor liver transplant cases (August 2015 to July 2019). The ABO-incompatible living donor liver transplant protocol involved rituximab administration (375 mg/m2 body surface area) at 2 to 3 weeks before transplant, subsequent plasma exchanges (target isoagglutinin titer of ≤1:8), basiliximab administration (20 mg on day of surgery and on postoperative day 4), and intravenous immunoglobulin administration (2 g/day from day of surgery to postoperative day 7). No graft local infusion therapy or splenectomy was performed. The living donor liver transplant procedure involved a modified rightlobe graft(18 patients), a right posterior segment graft (1 patient), or a left lobe (1 patient). The most common reason for liver transplant was hepatitis B virus-associated liver cirrhosis (16 patients); 14 patients had hepatocellular carcinoma. The mean age was 55.4 ± 6.3 years, mean Model End-stage LiverDisease score was 14.7 ± 7.7, and mean graft-to-recipient weight ratio was 1.07 ± 0.2%. The median initial anti-ABO antibody titers were 1:16 forimmunoglobulin M (range, 1:2 to 1:256) and 1:48 for immunoglobulin G (range, 1:4 to 1:>2048). The median number of plasma exchanges was 2 (range, 0-12). No patients had biopsy-confirmed antibody-mediated rejection. No bacterial or fungal infections were observed. Biliary anastomotic stricture was observed in 9 patients. This ABO-incompatible living donor liver transplant protocol with rituximab, plasma exchange, low-dose intravenous immunoglobulin, and immunosuppression (equivalent to ABO-compatible living donor liver transplant) could be a safe and effective way to overcome antibody-mediated rejection and other complications.

Effectiveness of low-dose intravenous immunoglobulin therapy in minor primary antibody deficiencies: A 2-year real-life experience.

Primary antibody deficiencies (PAD) are the most prevalent group of primary immunodeficiencies (PID) in adults and immunoglobulin replacement therapy (IRT) is the mainstay therapy to improve clinical outcomes. IRT is, however, expensive and, in minor PAD, clear recommendations concerning IRT are lacking. We conducted a retrospective real-life study to assess the effectiveness of low-dose IRT in minor PAD on 143 patients fulfilling European Society for Immunodeficiencies (ESID) diagnostic criteria for immunoglobulin (Ig)G subclass deficiency (IgGSD) or unclassified antibody deficiency (UAD). All patients were treated with intravenous low-dose IRT (0.14±0.06 g/kg/month). Immunoglobulin (Ig) classes and IgG subclasses were measured at baseline and after 1year of IRT. The annual rate of total infections, upper respiratory tract infections (URTI), lower respiratory tract infections (LRTI) and hospitalizations was measured at baseline and after 1 and 2 years of IRT. After 1 year of IRT significant improvement was demonstrated in: (a) serum IgG (787.9±229.3 versus 929.1±206.7mg/dl; p<0.0001); (b) serum IgG subclasses (IgG1=351.4±109.9 versus 464.3±124.1, p<0.0001; IgG2=259.1±140 versus 330.6±124.9, p<0.0001; IgG3=50.2±26.7 versus 55.6±28.9mg/dl, p<0.002); (c) annual rate of total infections (5.75±3.87 versus 2.13±1.74, p<0.0001), URTI (1.48±3.15 versus 0.69±1.27; p<0.005), LRTI (3.89±3.52 versus 1.29±1.37; p<0.0001) and hospitalizations (0.37±0.77 versus 0.15±0.5; p<0.0002). The improvement persisted after 2 years of IRT. No significant improvement in URTI annual rate was noted in UAD and in patients with bronchiectasis. In conclusion, low-dose IRT can improve clinical outcomes in UAD and IgGSD patients, providing a potential economical advantage over the standard IRT dose.

Stratified therapy for Kawasaki disease using a new scoring system to predict the response to a lower dose of intravenous immunoglobulin therapy.

Several studies have reported treatment options for patients with Kawasaki disease refractory to standard immunoglobulin therapy; however, no studies have reported low-dose immunoglobulin therapy for patients with a low risk of Kawasaki disease. A total of 277 patients with Kawasaki disease were included in this study. We used Kobayashi score and our Less high-risk score to divide the patients into three groups. Patients in the high-risk group (Kobayashi score ≥ 5 points) received 2 g/kg intravenous immunoglobulin and prednisolone. Patients in the moderate-risk group (Kobayashi score < 5 points and Less high-risk score ≥ 2 points) received 2 g/kg intravenous immunoglobulin treatment. Patients in the low-risk group (Kobayashi score < 5 points and Less high-risk score < 2 points) received 1 g/kg intravenous immunoglobulin treatment. The response rate and the incidence of coronary artery lesions at 4 weeks after treatment were evaluated in each group. The treatment response rates in the high-risk (n = 110), moderate-risk (n = 80), and low-risk (n = 87) groups were 74.5, 72.5, and 77.0%, respectively. Coronary artery lesions occurred in 7.3, 3.8, and 2.3% of patients in the high-, moderate-, and low-risk groups, respectively. There were no significant differences between the groups regarding treatment response or coronary artery lesion rate. The therapeutic response rate and the therapeutic effect of low-dose intravenous immunoglobulin in the low-risk group identified with our new scoring were satisfactory. Stratified therapies for patients with Kawasaki disease based on the scoring system may be useful.

Chronic low-dose intravenous immunoglobulins as steroid-sparing therapy in myasthenia gravis

Intravenous immunoglobulin (IVIg) has been proven beneficial in myasthenic crisis, but their role as maintenance therapy is unclear. The aim of this study was to determine if maintenance therapy with low-dose IVIg improves clinical outcome and may be used as a steroid-sparing agent in myasthenia gravis (MG). We retrospectively reviewed charts of all MG patients treated with IVIg from January 2006 to December 2019. Long-term treatment response to IVIg was assessed by improvement in the Myasthenia Gravis Foundation of America (MGFA) clinical classification scale as primary end point, as well as the ability to reduce the time-weighted average required dose of prednisone as secondary end-point, in a follow-up period of 36months. 109 patients were treated with IVIg. The mean follow-up time was 34.03 ± 5.5months. Sixty-seven patients (61.4%) responded to therapy with at least one-point improvement of the MGFA scale. There was no statistical difference in demographic and clinical characteristics between IVIg responders and non-responders. The mean prednisone dose decreased significantly from 33.1 ± 14.5mg at baseline to 7.2 ± 7.8mg after 36months of IVIg treatment (P < 0.0001), with the greatest effect after 6months (33.1 ± 14.5mg Vs. 17.9 ± 11.7mg; P < 0.0001). In the follow-up period of 36months, most patients (92.5%) remained clinically and pharmacologically stable under chronic IVIg treatment. This retrospective study demonstrates that chronic low-dose IVIg treatment in patients with MG improves clinical outcomes and has a prolonged and significant steroid-sparing effect over a period of 3years.

HLA Desensitization Based on Results of the Luminex Technique in Kidney Transplant - A Single-center Experience.

Background:There is little experience of human leucocyte antigen (HLA) desensitization in India based on the Luminex single-antigen bead (SAB) testing. We retrospectively analyzed our patients, who underwent HLA desensitization based on Luminex SAB results.Method:Between 2014 and 2018, patients with complement-dependent cytotoxicity cross-match (CDC-XM) negativity but flow cytometry crossmatch (FC-XM) positivity were further analyzed with Luminex SAB for donor-specific antibodies (DSAs). A total of 12 patients who had DSA mean fluorescent intensity (MFI) of >1000 and <10,000 were included in the study. Our protocol for desensitization consisted of plasmapheresis (PP) followed by low dose intravenous immunoglobulin (IV IG) 100 mg/kg and induction with antithymocyte globulin (ATG). Patients were taken for transplant when either MFI was <1000 and/or FC-XM was negative.Results:All 12 patients were first transplant and 10 had a history of some sensitizing event; pregnancy in 4, blood transfusions in 4, and both in 2 patients. FC-XM was positive for T-cell in 4, B-cell in 6, and both in 2 patients. On evaluation by Luminex SAB, 6 patients had MFI from 1000 to 2000, and 6 had MFI of >2000. All underwent desensitization successfully. Two patients had an increase in posttransplant DSA titers requiring posttransplant PP. The mean follow-up was 26.6 ± 13.9 months. On follow-up, only one patient developed acute T cell-mediated rejection 1 year after transplant, which responded to pulse steroids. There was no graft or patient loss until the last follow-up.Conclusion:This study shows that HLA desensitization is feasible and successful in the Indian setting if patients are properly selected.

Double-Filtration Plasmapheresis Plus Low-Dose Anti-thymocyte Globulin and Tacrolimus in Asian Living-Donor Kidney Transplantation With Donor-Specific Anti-HLA Antibody

BackgroundPretransplant desensitization protocols, including plasmapheresis, intravenous immunoglobulin, induction antibody therapy, and intensive maintenance immunosuppression, are generally employed in kidney transplant recipients who have positive status for donor-specific anti-HLA antibody (DSA). To avoid serious infectious complications, the authors designed a novel low-dose protocol in Thai patients undergoing DSA+ living-related kidney transplantation (LRKT). MethodsA retrospective cohort study of the patients who underwent DSA+ LRKT was conducted. The novel protocol consisted of 3 to 5 sessions of pretransplant double-filtration plasmapheresis (DFPP) with or without low-dose intravenous immunoglobulin together with low-dose anti-thymocyte globulin (ATG) induction (1-1.5 mg/kg/d for 3-4 days) and low-dose tacrolimus (Tac) (trough level 5-10 ng/mL), mycophenolate, and prednisolone. ResultsThe study included 17 patients. The lymphocyte crossmatch via complement-dependent cytotoxicity was negative in 12 patients and positive for B cell immunoglobulin M in 5 patients. The novel desensitization protocol resulted in a decrease of at least 50% of DSA mean fluorescence intensity from baseline (from 4320 ± 549 before DFPP to 1601 ± 350 before transplantation, P < .005) and successful kidney transplantation with good allograft function in all cases. Early DSA rebound was observed in 3 patients after transplantation, and kidney biopsy revealed subclinical antibody-mediated rejection in 1 patient and diffuse C4d staining without cell infiltration in 2 patients. There were good long-term outcomes in patient and graft survival (100% and 94.1%, respectively). Only 1 allograft loss occurred because of nonadherence. The majority of patients have stable allograft function with serum creatinine less than 1.5 mg/dL. However, infections, including CMV and other organisms, were commonly observed. ConclusionsDesensitization protocol with DFPP, low-dose ATG, and Tac provides excellent outcomes in living donor kidney transplantation in highly sensitized Asian populations.

High-dose versus low-dose intravenous immunoglobulin for treatment of children with Kawasaki disease weighing 25 kg or more.

Little is known whether 2-g/kg IVIG is necessary for older children with Kawasaki disease (KD), because they could have more complications and financial burden. The purpose of this study was to compare outcomes between high- and low-dose IVIG in KD children with higher body weight (25 kg or more), using a national inpatient database in Japan from 2010 to 2017. We identified those receiving 2-g/kg and 1-g/kg IVIG as an initial treatment. Outcomes included the proportions of coronary artery abnormality (CAA) formation, IVIG resistance, adverse effects, length of stay, and medical costs. A propensity score matching analysis was conducted to compare the outcomes between the groups. We identified 1332 patients with KD and created 4:1 propensity score-matched pairs between high- and low-dose IVIG groups. There were no significant differences in the proportions of CAA (5.3% vs. 4.1%; p = 0.587), IVIG resistance, and length of stay. Medical costs were significantly higher in the high-dose group than in the low-dose group (p < 0.001).Conclusion: No significant difference was shown between the high- and low-dose IVIG groups in the proportions of outcomes, while medical costs were higher in the high-dose group. Further studies are needed to ascertain the appropriate IVIG dose in older patients with KD. What is Known: • For treatments of Kawasaki disease at any age in the acute phase, 2-g/kg single-dose intravenous immunoglobulin and aspirin have been the most recommended to reduce fever early and prevent complications of coronary artery abnormalities. What is New: • There was no significant difference in outcomes between children with Kawasaki disease weighing ≥ 25 kg treated with high-dose or low-dose IVIG in terms of coronary artery abnormalities, IVIG resistance, adverse effects, and length of stay, except for medical costs.

AMBAR, an Encouraging Alzheimer's Trial That Raises Questions.

Grifols' recent Alzheimer Management by Albumin Replacement (“AMBAR”) study investigated the effects of plasmapheresis with albumin replacement, plus intravenous immunoglobulin (IVIG) in some subjects, in patients with mild-to-moderate Alzheimer's disease (AD). AMBAR was a phase IIb trial in the United States and a phase III trial in Europe. There were three treatment groups (plasmapheresis with albumin replacement; plasmapheresis with low dose albumin and IVIG; plasmapheresis with high dose albumin and IVIG) and sham-treated controls. Disease progression in pooled treated patients was 66% less than control subjects based on ADAS-Cog scores (p = 0.06) and 52% less based on ADCS-ADL scores (p = 0.03). Moderate AD patients had 61% less progression, based on both ADAS-Cog and ADCS-ADL scores, than their sham-treated counterparts (p-values 0.05 and 0.002), and their CDR-Sb scores declined 53% less than their sham-treated counterparts. However, ADAS-Cog and ADCS-ADL scores were not significantly different between actively-treated and sham-treated mild AD patients, although CDR-Sb scores improved vs. baseline for treated mild AD patients. Patients administered both IVIG and albumin had less reduction in brain glucose metabolism than sham-treated patients. Questions raised by these findings include: what mechanism(s) contributed to slowing of disease progression? Is this approach as effective in mild AD as in moderate AD? Must IVIG be included in the protocol? Does age, sex, or ApoE genotype influence treatment response? Does the protocol increase the risk for amyloid-related imaging abnormalities? How long does disease progression remain slowed post-treatment? A further study should allow this approach to be optimized.

Low dose intravenous immunoglobulin in addition to cyclophosphamide in systemic sclerosis : Single centre experience.

Systemic sclerosis (SSc) is arare chronic disease characterized by pathologic collagen deposits in the skin and internal organs. Although it is considered to be an autoimmune disease, immunosuppressants have alimited effect on severe SSc. Intravenous immunoglobulins (IVIG) have shown favorable effects in patients with SSc by suppressing the action of profibrotic cytokines, so they could have additional effect on standard treatment such as cyclophosphamide (CYC). This article presents the immunomodulatory effect of low-dose IVIG in addition to CYC in the treatment of severe SSc in this center during the last 9years. This retrospective observational study analyzed the medical documentation of nine patients with SSc treated with low-dose IVIG (0.4 g/kg and month) together with intravenous CYC (600 mg/m2 and month). The therapeutic effect on lung and skin manifestations was assessed. Of the patients one had interstitial lung diseases (ILD), two had progressive skin diseases, and six had a combination of skin and lung involvement. The best results were achieved in skin changes, where complete healing of digital ulcers (DU) was recorded in every reported case. A decrease in the modified Rodnan skin score (mRSS) was noted in three patients and increased diffusion capacity of the lungs for carbon monoxide in another three patients. The results of the study suggest that IVIG may be an additional treatment option together with CYC for patients for whom other therapies have failed, but further studies on the exact role of IVIG in the treatment of severe SSc are required.

Multiple interferences of serologic studies in an Epstein–Barr virus-related infectious mononucleosis

Epstein–Barr virus (EBV) infection is a common infectious disease in young adults and children. A 4-year-old boy was presented with enlarged tonsils and purulent discharge. Sudden airway collapse and desaturation were noted, and endotracheal tube intubation was performed. The laboratory data demonstrated positive results for EBV immunoglobulin M (IgM). Polyclonal B-cell activation that led to positive results for cytomegalovirus (CMV) IgM and herpes simplex virus (HSV) IgM was also detected by the interference of heterophilic antibodies. A low-dose intravenous immunoglobulin (IVIG) infusion was performed, and an IVIG-related false-positive result for CMV immunoglobulin G (IgG) was observed. After the aggressive medical care, the boy was discharged under a stable condition. Herein, we report the important features of EBV-related infectious mononucleosis that harvested multiple interferences. First, the heterophilic antibodies caused due to polyclonal B-cell activation resulted in the false-positive result for CMV IgM and HSV IgM. Second, the IVIG interpreted the CMV IgG. We must be aware of the multiple interferences that could misinterpret our laboratory data.

Predictors of graft survival at diagnosis of antibody-mediated renal allograft rejection: a retrospective single-center cohort study.

Antibody-mediated rejection (ABMR) is a major cause of graft loss in renal transplantation. We assessed the predictive value of clinical, pathological, and immunological parameters at diagnosis for graft survival. We investigated 54 consecutive patients with biopsy-proven ABMR. Patients were treated according to our current standard regimen followed by triple maintenance immunosuppression. Patient characteristics, renal function, and HLA antibody status at diagnosis, baseline biopsy results, and immunosuppressive treatment were recorded. The risk of graft loss at 24months after diagnosis and the eGFR slope were assessed. Multivariate analysis showed that eGFR at diagnosis and chronic glomerulopathy independently predict graft loss (HR 0.94; P=0.018 and HR 1.57; P=0.045) and eGFR slope (beta 0.46; P<0.001 and beta -5.47; P<0.001). Cyclophosphamide treatment (6× 15mg/m2 ) plus high-dose intravenous immunoglobulins (IVIG) (1.5g/kg) was superior compared with single-dose rituximab (1× 500mg) plus low-dose IVIG (30g) (HR 0.10; P=0.008 and beta 10.70; P=0.017) and one cycle of bortezomib (4× 1.3mg/m2 ) plus low-dose IVIG (HR 0.16; P=0.049 and beta 11.21; P=0.010) regarding the risk of graft loss and the eGFR slope. In conclusion, renal function at diagnosis and histopathological signs of chronic ABMR seem to predict graft survival independent of the applied treatment regimen. Stepwise modifications of the treatment regimen may help to improve outcome.