Spleen autotransplantation provides restoration of functional splenic lymphoid compartments and improves the humoral immune response to pneumococcal polysaccharide vaccine

Leemans, R.; Harms, Geert; Rijkers, G.T.; Timens, Wim

doi:10.1046/j.1365-2249.1999.00943.x

Cited by 50 publications

(51 citation statements)

References 30 publications

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“…However, it has to be stressed that the ability of such patients to produce antipolysaccharide antibodies that are involved in humoral defense against encapsulated bacteria and are synthesized by a splenic B-lymphocyte subpopulation has still to be evaluated. 24,25 Obvious clinical benefits could be documented in patients with HS after subtotal splenectomy. In our experience, chronic discomfort that does not correlate with the intensity of anemia is a frequent finding in untreated patients with HS.…”

Section: Discussionmentioning

confidence: 99%

Long-term evaluation of the beneficial effect of subtotal splenectomy for management of hereditary spherocytosis

Bader-Meunier

Gauthier

Archambaud

et al. 2001

Blood

144

112

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Clinical manifestations of hereditary spherocytosis (HS) can be abrogated by splenectomy. However, concerns exist regarding exposure of patients to a lifelong risk for overwhelming infections and, to a lesser extent, to vascular complications after total splenectomy. In the search for alternative treatment modalities, we assessed, in a previous pilot study, the potential usefulness of subtotal splenectomy in a small population of patients. During a mean follow-up period of 3.5 years, subtotal splenectomy was shown to be effective in decreasing the hemolytic rate, while maintaining the phagocytic function of the spleen. In the current study, we evaluated the clinical and biologic features of 40 patients with HS who underwent subtotal splenectomy and were monitored for periods ranging from 1 to 14 years. The beneficial effect of subtotal splenectomy included a sustained decrease in hemolytic rate and a continued maintenance of phagocytic function of the splenic remnant. However, mild-to-moderate hemolysis was persistent and accounted for secondary gallstone formation and aplastic crisis in a small subset of patients. Surprisingly, regrowth of the remnant spleen did not seem to have a major impact on the beneficial outcomes of these individuals. Our results suggest that subtotal splenectomy appears to be a reasonable treatment option for management of patients with HS, especially young children.

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Section: Discussionmentioning

confidence: 99%

Long-term evaluation of the beneficial effect of subtotal splenectomy for management of hereditary spherocytosis

Bader-Meunier

Gauthier

Archambaud

et al. 2001

Blood

144

112

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“…We used a rat model for which it was previously shown that splenectomy had a clearly negative effect on the antipolysaccharide antibody response (21). Because PCV contain only a limited number (4 to 11) of pneumococcal serotypes compared with the number contained by 23-valent PPS vaccines, we studied the potential benefit of admixture of additional polysaccharides with the PCV.…”

mentioning

confidence: 99%

Pneumococcal Conjugate Vaccines Overcome Splenic Dependency of Antibody Response to Pneumococcal Polysaccharides

Breukels

Zandvoort²,

Dobbelsteen

et al. 2001

Infect Immun

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Protection against infections with Streptococcus pneumoniae depends on the presence of antibodies against capsular polysaccharides that facilitate phagocytosis. Asplenic patients are at increased risk for pneumococcal infections, since both phagocytosis and the initiation of the antibody response to polysaccharides take place in the spleen. Therefore, vaccination with pneumococcal polysaccharide vaccines is recommended prior to splenectomy, which, as in the case of trauma, is not always feasible. We show that in rats, vaccination with a pneumococcal conjugate vaccine can induce good antibody responses even after splenectomy, particularly after a second dose. The spleen remains necessary for a fast, primary response to (blood-borne) polysaccharides, even when they are presented in a conjugated form. Coadministration of a conjugate vaccine with additional nonconjugated polysaccharides of other serotypes did not improve the response to the nonconjugated polysaccharides. We conclude that pneumococcal conjugate vaccines can be of value in protecting asplenic or hyposplenic patients against pneumococcal infections.Protection against infections with encapsulated bacteria such as Streptococcus pneumoniae depends on the presence of antibodies against capsular polysaccharides. These serotypespecific antibodies facilitate phagocytosis, the main mode of host defense against S. pneumoniae. The spleen is an important organ in the immune response to S. pneumoniae, since it contains both antibody-producing B cells and phagocytes (4, 26). Asplenic patients are therefore at increased risk for invasive infections with S. pneumoniae (13). Although most infections occur within the first few years after splenectomy, the risk of overwhelming postsplenectomy infections is lifelong (9, 36). Therefore, vaccination against S. pneumoniae is indicated for this group. At present, the vaccine available for this aim is the 23-valent pneumococcal polysaccharide (PPS) vaccine (1). The immunogenicity of PPS vaccine in splenectomized patients has been assessed in a number of trials. Some studies have shown the effectiveness of vaccination in inducing protective concentrations of specific antibodies (5, 10, 24, 33), while others have shown limited serological responses (15). As the initiation of the antibody response to polysaccharides seems to depend on the presence of splenic tissue, and in particular on a functional marginal-zone B-cell compartment (3,14,18,34), it may be expected that polysaccharide vaccines are of limited use in asplenic patients.The physical coupling of a polysaccharide to a carrier protein greatly improves the immunogenicity of the polysaccharide, a principle first described in 1929 (11). Conjugated polysaccharides overcome the antipolysaccharide unresponsiveness in early life (2, 8), which is thought to be due to a still immature splenic marginal-zone B-cell compartment (2). The induction of antipolysaccharide antibodies by conjugate vaccines at a young age suggests that conjugates might initiate the antipolysaccharide anti...

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“…Hence, autotransplantation or maintenance of residual splenic tissue is now standard practice [91]. Vaccinations against encapsulated organisms are administered to manage these two cohorts showing physical and/or functional impairment of the splenic marginal zone, however, the use of conjugate vaccines (where available) in these cases appears to be more justified than that of polysaccharide antigens.…”

Section: Discussionmentioning

confidence: 99%

The role of complement in the success of vaccination with conjugated vs. unconjugated polysaccharide antigen

Salehen¹,

Stover²

2008

Vaccine

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The complement system, a well-characterised arm of the innate immune system, significantly influences the adaptive immune response via direct cell-cell interaction and maintenance of lymphoid organ architecture. Development of vaccines is a major advance in modern health care. In this review, we highlight the importance of the marginal zone in response to both, polysaccharide and conjugated vaccines, and discuss the relevance of complement herein, based on findings obtained from animal models with specific deletions of certain complement components and from vaccination reports of complement-deficient individuals. We conclude that both, intactness of the complement system and maturity of expression of its components, are relatively more important to aid in the immune response to polysaccharide vaccine than to conjugated vaccines. keywords (3): complement vaccine polysaccharide running titleComplement essential for polysaccharide vaccines 2 The importance of complement activation in adaptive immunityThe complement system is part of the innate immune defence, because it partakes in first-line, pattern-mediated recognition via its germ-line encoded serum proteins and receptors. It has evolved from a primordial fluid-phase system that "simply" tags and mediates uptake of micro-organisms by cells of early chordates. Large-scale gene duplications, exon shuffling and transposition events are the main evolutionary mechanisms that have generated a wide range of diversified molecules, which we now ascribe to innate and adaptive immune defences Importantly, after subcutaneous administration of T-independent or T-dependent antigens in mice, it is the spleen that reacts with formation of antibody forming cells before the draining lymphnodes, especially in response to T-independent antigen [32].Germinal centers are formed during an immune response elicited with a so-called Tindependent antigen. This reaction is, however, of short duration. It is possible that the absence of somatic hypermutation of the immunoglobulin V genes is due to both, the curtailed germinal center reaction -as somatic hypermutation is a relatively late event -6 and the lack of T-cell help [33]. Of note, marginal zone B-cells are incapable of participating in the process of somatic hypermutation due to the lack of expression of activation-induced cytidine deaminase, an enzyme essential for this process [34].The involvement of T-cells is not strictly excluded in the antibody response against polysaccharides, as B7 ligand dependent costimulation of B-cells (by T-cells) is needed, however, the interaction in this early response is short and T-cell receptor unspecific [35].The absence of somatic hypermutation does, however, explain the low affinity binding of anti-polysaccharide antibodies.

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Spleen autotransplantation provides restoration of functional splenic lymphoid compartments and improves the humoral immune response to pneumococcal polysaccharide vaccine

Cited by 50 publications

References 30 publications

Long-term evaluation of the beneficial effect of subtotal splenectomy for management of hereditary spherocytosis

Long-term evaluation of the beneficial effect of subtotal splenectomy for management of hereditary spherocytosis

Pneumococcal Conjugate Vaccines Overcome Splenic Dependency of Antibody Response to Pneumococcal Polysaccharides

The role of complement in the success of vaccination with conjugated vs. unconjugated polysaccharide antigen

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