Background Labral refixation rather than resection provides better pain relief and function after femoroacetabular impingement (FAI) surgery.

T cell-dependent B cell responses typically develop in germinal centers. Abs generated during such responses are isotype switched and have a high affinity to the Ag because of somatic hypermutation of Ab genes. B cell responses to purified polysaccharides are T cell independent and do not result in the formation of bona fide germinal centers, and the dominant Ab isotype produced during such responses is IgM with very few or no somatic mutations. Activation-induced cytidine deaminase (AID) is required for both somatic hypermutation and Ig isotype switching in humans and mice. To test the extent to which unmutated polysaccharide-specific IgM confers protective immunity, we immunized wildtype and AID mice with either heat-killed serovar Typhi ( Typhi) or purified Vi polysaccharide (ViPS). We found that wildtype and AID mice immunized with heat-killed Typhi generated similar anti-ViPS IgM responses. As expected, wildtype, but not AID mice generated ViPS-specific IgG. However, the differences in the Ab-dependent killing of Typhi mediated by the classical pathway of complement activation were not statistically significant. In ViPS-immunized wildtype and AID mice, the ViPS-specific IgM levels and Typhi bactericidal Ab titers at 7 but not at 28 d postimmunization were also comparable. To test the protective immunity conferred by these immunizations, mice were challenged with a chimeric Typhimurium strain expressing ViPS. Compared with their naive counterparts, immunized wildtype and AID mice exhibited significantly reduced bacterial burden regardless of the route of infection. These data indicate that an unmutated IgM response to ViPS contributes to protective immunity to Typhi.

Polysaccharide vaccines such as the Vi polysaccharide (ViPS) of serovar Typhi induce efficient Ab responses in adults but not in young children. The reasons for this difference are not understood. IL-7 dependency in B cell development increases progressively with age. IL-7Rα-mediated signals are required for the expression of many V gene segments that are distal to D-J in the IgH locus and for the complete diversification of the BCR repertoire. Therefore, we hypothesized that B cells generated in the absence of IL-7 do not recognize a wide range of Ags because of a restricted BCR repertoire. Compared with adult wildtype mice, young wildtype mice and IL-7-deficient adult mice generated a significantly reduced Ab response to ViPS. Additionally, ViPS-binding B cells in adult wildtype mice predominantly used distal V gene segments. Transgenic expression of either IL-7 or a BCR encoded by a distal V gene segment permitted young mice to respond efficiently to bacterial polysaccharides. These results indicate that restricted V gene usage early in life results in a paucity of Ag-specific B cell precursors, thus limiting antipolysaccharide responses.

Circulating IgM present in the body prior to any apparent Ag exposure is referred to as natural IgM. Natural IgM provides protective immunity against a variety of pathogens. Salmonella enterica serovar Typhi (S. Typhi) is the causative agent of typhoid fever in humans. Because mice are not permissive to S. Typhi infection, we employed a murine model of typhoid using S. enterica serovar Typhimurium expressing the Vi polysaccharide (ViPS) of S. Typhi (S. Typhimurium strain RC60) to evaluate the role of natural IgM in pathogenesis. We found that natural mouse IgM binds to S. Typhi and S. Typhimurium. The severity of S. Typhimurium infection in mice is dependent on presence of the natural resistance-associated macrophage protein 1 (Nramp1) allele; therefore, we infected mice deficient in secreted form of IgM (sIgM) on either a Nramp1-resistant (129S) or -susceptible (C57BL/6J) background. We found that the lack of natural IgM results in a significantly increased susceptibility and an exaggerated liver pathology regardless of the route of infection or the Nramp1 allele. Reconstitution of sIgM−/− mice with normal mouse serum or purified polyclonal IgM restored the resistance to that of sIgM+/+ mice. Furthermore, immunization of sIgM−/− mice with heat-killed S. Typhi induced a significantly reduced anti-ViPS IgG and complement-dependent bactericidal activity against S. Typhi in vitro, compared with that of sIgM+/+ mice. These findings indicate that natural IgM is an important factor in reducing the typhoid severity and inducing an optimal anti-ViPS IgG response to vaccination.

Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

The success rate for achieving knee stability in primary anterior cruciate ligament (ACL) reconstruction is high; however, the results of revision reconstruction are less satisfactory. Sagittal plane malalignment is an uncommon predisposing factor for failure because excessive posterior tibial slope increases stress on the ACL graft. In carefully selected patients, tibial slope correction is an essential adjunctive procedure to achieve a stable knee. We present a case report outlining the surgical technique for correction of sagittal plane imbalance by a slope-decreasing anterior closing wedge tibial osteotomy combined with a second-stage revision ACL reconstruction. At 2 years following surgery, our patient had a stable knee and returned to low-impact athletic activity without symptoms. Further investigation is needed to refine the indications for this procedure in the setting of failed ACL reconstruction.

B cell antigen receptor (BCR) diversity increases by several orders of magnitude due to the action of terminal deoxynucleotidyl transferase (TdT) during V(D)J recombination. Unlike adults, infants have limited BCR diversity, in part due to reduced expression of TdT. Since human infants and young mice respond poorly to polysaccharide vaccines, such as the pneumococcal polysaccharide vaccine Pneumovax23 and Vi polysaccharide (ViPS) of serovar Typhi, we tested the contribution of TdT-mediated BCR diversity in response to these vaccines. We found that TdT and TdT mice generated comparable antibody responses to Pneumovax23 and survived challenge. Moreover, passive immunization of B cell-deficient mice with serum from Pneumovax23-immunized TdT or TdT mice conferred protection. TdT and TdT mice generated comparable levels of anti-ViPS antibodies and antibody-dependent, complement-mediated bactericidal activity against Typhi To test the protective immunity conferred by ViPS immunization , TdT and TdT mice were challenged with a chimeric serovar Typhimurium strain expressing ViPS, since mice are nonpermissive hosts for Typhi infection. Compared to their unimmunized counterparts, immunized TdT and TdT mice challenged with ViPS-expressing Typhimurium exhibited a significant reduction in the bacterial burden and liver pathology. These data suggest that the impaired antibody response to the Pneumovax23 and ViPS vaccines in the young is not due to limited TdT-mediated BCR diversification.

ObjectivesSustained intra-articular delivery of pharmacological agents is an attractive modality but requires use of a safe carrier that would not induce cartilage damage or fibrosis. Collagen scaffolds are widely available and could be used intra-articularly, but no investigation has looked at the safety of collagen scaffolds within synovial joints. The aim of this study was to determine the safety of collagen scaffold implantation in a validated in vivo animal model of knee arthrofibrosis.Materials and MethodsA total of 96 rabbits were randomly and equally assigned to four different groups: arthrotomy alone; arthrotomy and collagen scaffold placement; contracture surgery; and contracture surgery and collagen scaffold placement. Animals were killed in equal numbers at 72 hours, two weeks, eight weeks, and 24 weeks. Joint contracture was measured, and cartilage and synovial samples underwent histological analysis.ResultsAnimals that underwent arthrotomy had equivalent joint contractures regardless of scaffold implantation (-13.9° versus -10.9°, equivalence limit 15°). Animals that underwent surgery to induce contracture did not demonstrate equivalent joint contractures with (41.8°) or without (53.9°) collagen scaffold implantation. Chondral damage occurred in similar rates with (11 of 48) and without (nine of 48) scaffold implantation. No significant difference in synovitis was noted between groups. Absorption of the collagen scaffold occurred within eight weeks in all animalsConclusionOur data suggest that intra-articular implantation of a collagen sponge does not induce synovitis or cartilage damage. Implantation in a native joint does not seem to induce contracture. Implantation of the collagen sponge in a rabbit knee model of contracture may decrease the severity of the contracture.Cite this article: J. A. Walker, T. J. Ewald, E. Lewallen, A. Van Wijnen, A. D. Hanssen, B. F. Morrey, M. E. Morrey, M. P. Abdel, J. Sanchez-Sotelo. Intra-articular implantation of collagen scaffold carriers is safe in both native and arthrofibrotic rabbit knee joints. Bone Joint Res 2016;6:162–171. DOI: 10.1302/2046-3758.63.BJR-2016-0193.