Solid organ transplantation: hypogammaglobulinaemia and infectious complications after solid organ transplantation

Abstract

Hypogammaglobulinaemia (HGG), defined as a serum immunoglobulin G (IgG) level < 700 mg/dl, is a known complication of solid organ transplantation (SOT), with a high prevalence reported following heart, lung and kidney transplantation [1,2]. HGG is associated with an increased risk of infection, which depends upon the degree of HGG, the type of allograft and the intensity of immunosuppression [1,2]. Although all agents used for maintenance immunosuppression have a direct effect on T cell function and an indirect effect on B cell function and lymphokine production, some immunosuppressive agents (e.g. mycophenolate mofetil) have a more potent inhibitor effect on B lymphocyte proliferation and antibody production and may result in more pronounced HGG [1,3]. HGG can occur following induction therapy, maintenance immunosuppressive regimens or treatment of rejection episodes [1]. Monitoring serum IgG levels before and after SOT has been proposed as a tool to predict clinical outcomes; however, the conclusions of the published studies have been limited by the relatively small sample size. Therefore, our group from the University of Nebraska carried out a meta-analysis to evaluate the prevalence of HGG after SOT and its impact on the rate of opportunistic infections during the first year posttransplantation [1]. This meta-analysis included 18 studies (1756 patients), with a mean age of 42 years [95% confidence interval (CI) = 30·9-53·1; Q-statistic = 8249·87; 15 studies, 1232 patients], 43% of whom were female (95% CI = 0·35-0·50; Q = 93·04; 14 studies, 1140 patients) [1]. HGG (serum IgG < 700 mg/dl) was found to be highly prevalent, occurring in 45% of transplant recipients in the first year post-transplantation (95% CI = 0·34-0·55; Q = 329·63; P < 0·0001; 16 studies, 1482 patients), while severe HGG (defined as serum IgG < 400 mg/dl) was less common, occurring in only 15% of transplant recipients (95% CI = 0·08-0·22; Q statistic = 210·09, P < 0·0001; eight studies, 669 patients) [1]. The heterogeneity of the studies included in the meta-analysis was high, most likely due to inherent differences in individual studies, such as the inclusion of both paediatric and adult studies, variation in study design and the inclusion of different allografts. Subset analysis showed a much higher rate of HGG in heart (49%), lung (63%) and kidney (40%) transplant recipients compared with liver transplant recipients (16%) [1].No studies evaluating HGG after intestinal transplantation were included in the meta-analysis, and there are limited data available. A recent publication from Farmer et al. indicates that the rate of HGG may be high in these patients (59%) [4]. This study retrospectively evaluated 34 intestinal transplant recipients, with a mean age of 12·4 years (standard deviation 17·2), 76% of whom were paediatric patients and 62% were male [4]. Serum IgG levels were measured at the time of evaluation, at the time of transplantation and at weekly intervals for 2 months posttransplant [4]. Serum IgG fell quickly in the first week ...

Clinical outcomes of immunoglobulin treatment for patients with secondary antibody deficiency: Data from the Ontario immunoglobulin treatment case registry

“…Frequency of hypogammaglobulinemia can be different in different types of SOT. For instance, SAD is prevalent in 63% of lung transplant recipients in the first-year posttransplant, compared to 45% and 30% of patients, at 3 and 12 months post-renal transplantation, respectively [23]. However, there were more kidney transplant than lung transplant recipients of IgRT in our cohort.…”

“…In our study, there were 11 SAD patients who were SOT recipients. In the published literature, Ig deficiency developed in 45% of patients 1-year post-transplantation while there was severe Ig deficiency (IgG <4 g/L) in 15% of all transplant recipients [23]. The latter was associated with an increased risk of infection and 1-year all-cause mortality.…”

Intravenous immunoglobulin in heart transplant recipients with mild to moderate hypogammaglobulinemia and infection

“…Induction agents for transplantation, maintenance immunosuppressive therapy, and treatment of rejection episodes predispose transplant recipients to HGG 2 . Heart transplant recipients with HGG, specifically, have been found to have an increased risk of respiratory tract infections, cytomegalovirus (CMV), Clostridioides difficile , Aspergillus , and other infections, along with higher post‐transplant mortality 5,6 …”

“…2 Heart transplant recipients with HGG, specifically, have been found to have an increased risk of respiratory tract infections, cytomegalovirus (CMV), Clostridioides difficile, Aspergillus, and other infections, along with higher post-transplant mortality. 5,6 Few studies have evaluated the use of intravenous immunoglobulin G (IVIG) for heart transplant recipients with HGG and simultaneous documented infections. Available studies have either preemptively dosed IVIG in patients with HGG but no infections, 7 or given IVIG in the Clinical Transplantation.…”