The pathology of failed McKee-Farrar implants: correlation with modern metal-on-metal-implant failure.

The McKee-Farrar (MF) prosthesis was the first widely used total hip replacement (THR) to employ a metal-on-metal (MoM) articulation. These implants had a high rate of early aseptic loosening but a number achieved good long-term implant survival, stimulating the reintroduction of second and third generation implants of this type. In this study we analysed archival histopathology of periprosthetic tissues in twenty cases of MF aseptic implant failure to determine if there was evidence of an innate and adaptive immune response similar to that seen in modern MoM implants. The presence of macrophages, the extent of necrosis and the ALVAL response were graded semi-quantitatively. Variable but in most cases extensive tissue necrosis was associated with a heavy macrophage response to Cobalt-Chrome (Co-Cr) wear particles in periprosthetic tissues; most cases also contained evidence of a predominantly lymphocyte response which in eight cases was moderate or heavy (Oxford Grade 2/3). Our findings show that inflammatory and necrotic changes to deposition of Co-Cr wear particles are found in periprosthetic tissues of failed MF implants, indicating that there is an innate and adaptive response similar to that noted in second/third generation MoM implants; they also suggest that the pathobiological response to metal wear particles is likely to have contributed to MF implant failure in these cases.

Association between serum levels of the proinflammatory protein S100A8/A9 and clinical and structural characteristics of patients with established knee, hip, and hand osteoarthritis.

OBJECTIVES: To explore the association between S100A8/A9 serum levels with clinical and structural characteristics of patients with established knee, hip, or hand osteoarthritis (OA). METHOD: A cross-sectional exploratory study was conducted with 162 OA patients. Measures for pain, stiffness, and function included the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) questionnaire or the Australian Canadian Osteoarthritis Hand (AUSCAN) Index and for structural abnormalities, osteophytes and joint space narrowing grades. The association between S100A8/A9 and clinical or structural characteristics was analysed using linear regression or logistic regression where appropriate. RESULTS: The mean age of the OA patients was 56 years, 71% were female, and 61% had a Kellgren and Lawrence (K&L) score ≥ 2. The serum S100A8/A9 level did not differ between knee, hip, and hand OA patients and no association was found between serum S100A8/A9 and clinical characteristics. The serum S100A8/A9 level was negatively associated with the sum score of osteophytes after adjusting for sex and body mass index (BMI) [adjusted ß -0.015, 95% confidence interval (CI) -0.030 to 0.001, p = 0.062] and positively associated with erythrocyte sedimentation rate (ESR) > 12 mm/h (adjusted OR 1.002, 95% CI 1.000-1.004 p = 0.049) for each increase in S100A8/A9 of 1 ng/mL. For hand OA patients, a negative association of S100A8/A9 with sum score of joint space narrowing was found (adjusted ß -0.007, 95% CI -0.016 to 0.001, p = 0.099). CONCLUSIONS: The results from this cross-sectional exploratory study do not support an important role for serum S100A8/A9 levels as a biomarker for clinical and structural characteristics in established knee, hip, and hand OA patients. The inverse association with structural abnormalities and the positive association with ESR may reflect inflammatory synovial processes in patients with OA before structural abnormalities occur.

Molecular analysis of chromium and cobalt-related toxicity.

Occupational and environmental exposure to Co and Cr has been previously linked to a wide array of inflammatory and degenerative conditions and cancer. Recently, significant health concerns have been raised by the high levels of Cr and Co ions and corrosion products released by biomedical implants. Herein, we set to analyze the biological responses associated with Co and Cr toxicity. Histological, ultrastructural, and elemental analysis, performed on Cr and Co exposed patients reveal the presence of corrosion products, metallic wear debris and metal ions at varying concentrations. Metallic ions and corrosion products were also generated in vitro following macrophage phagocytosis of metal alloys. Ex vivo redox proteomic mapped several oxidatively damaged proteins by Cr(III) and Co(II)-induced Fenton reaction. Importantly, a positive correlation between the tissue amounts of Cr(III) and Co(II) ions and tissue oxidative damage was observed. Immobilized- Cr(III) and Co(II) affinity chromatography indicated that metal ions can also directly bind to several metallo and non-metalloproteins and, as demonstrated for aldolase and catalase, induce loss of their biological function. Altogether, our analysis reveals several biological mechanisms leading to tissue damage, necrosis, and inflammation in patients with Cr and Co-associated adverse local tissue reactions.

High metal ion levels after use of the ASR™ device correlate with development of pseudotumors and T cell activation.

BACKGROUND: Pseudotumors and immunologic alterations are reported in patients with elevated metal ion levels after resurfacing arthroplasty of the hip. A direct association of increased cobalt and chromium concentrations with the development of pseudotumors has not been established. QUESTIONS/PURPOSES: We hypothesized that (1) patients with higher blood cobalt and chromium concentrations are more likely to have pseudotumors develop, (2) elevated cobalt and chromium concentrations correlate with increased activation of defined T cell populations, and (3) elevated metal ion levels, small implant size, cup inclination angle, and patient age are risk factors for the development of pseudotumors. METHODS: A single-surgeon cohort of 78 patients with 84 Articular Surface Replacement(®) implants was retrospectively investigated. Between 2006 and 2010, we performed 84 THAs using the Articular Surface Replacement(®) implant; this represented 2% (84/4950) of all primary hip replacements performed during that period. Of the procedures performed using this implant, we screened 77 patients (99%) at a mean of 43 months after surgery (range, 24-60 months). Seventy-one patients were investigated using ultrasound scanning, and cobalt and chromium concentrations in whole blood were determined by high-resolution inductively coupled plasma mass spectrometry. Differential analysis of lymphocyte subsets was performed by flow cytometry in 53 patients. Results of immunologic analyses were investigated separately for patients with and without pseudotumors. Pseudotumors were found in 25 hips (35%) and were more common in women than in men (p = 0.02). Multivariable regression analysis was performed to identify risk factors for the development of pseudotumors. RESULTS: Cobalt and chromium concentrations were greater in patients with pseudotumors than in those without (cobalt, median 8.3 versus median 1.0 µg/L, p < 0.001; chromium, median 5.9 versus median 1.3 µg/L, p < 0.001). The percentage of HLA-DR(+)CD4(+) T cells was greater in patients with pseudotumors than in those without (p = 0.03), and the proportion of this lymphocyte subtype was positively correlated with cobalt concentrations (r = 0.3, p = 0.02). Multivariable regression analysis indicated that increasing cobalt levels were associated with the development of pseudotumors (p < 0.001), and that patients with larger implants were less likely to have them develop (p = 0.04); age and cup inclination were not risk factors. CONCLUSIONS: We found a distinct association of elevated metal ion concentrations with the presence of pseudotumors and a correlation of increased cobalt concentrations with the proportion of activated T helper/regulator cells. Thus, the development of soft tissue masses after metal-on-metal arthroplasty could be accompanied by activation of T cells, indicating that this complication may be partly immunologically mediated. Further investigations of immunologic parameters in larger cohorts of patients with metal-on-metal arthroplasties are warranted. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.

Effects of icariin on cytokine-induced ankylosing spondylitis with fibroblastic osteogenesis and its molecular mechanism.

The aim of this study is to explore the effects of icariin on cytokine induced ankylosing spondylitis fibroblast osteogenesis type expression and its molecular mechanism. The normal fibroblasts were collected as normal control group, and the fibroblasts of hip joint capsule of AS patients were collected, which were respectively added in fetal bovine serum (group AS), fetal bovine serum and cytokines (BMP-2+TGF-beta 1) (group AS), and cell factor solution (icariin group), and observed of the osteogenic expression of fibroblast, to evaluate the impact of Icariin on it. The ALP activity, the content of collagen, osteocalcin content and cbfa1mRNA and OCmRNA of fibroblast of AS group increased compared to the normal control group and AS control group (P < 0.01), indicating that icariin can significantly inhibit the above changes (P < 0.01). Icariin can inhibit fibroblast further osteogenic differentiation through inhibiting the effect of cytokines on the fibroblast osteogenesis type markers and osteogenic gene expression and osteogenic differentiation.

Cobalt-alloy implant debris induce HIF-1α hypoxia associated responses: a mechanism for metal-specific orthopedic implant failure.

The historical success of orthopedic implants has been recently tempered by unexpected pathologies and early failures of some types of Cobalt-Chromium-Molybdenum alloy containing artificial hip implants. Hypoxia-associated responses to Cobalt-alloy metal debris were suspected as mediating this untoward reactivity at least in part. Hypoxia Inducible Factor-1α is a major transcription factor involved in hypoxia, and is a potent coping mechanism for cells to rapidly respond to changing metabolic demands. We measured signature hypoxia associated responses (i.e. HIF-1α, VEGF and TNF-α) to Cobalt-alloy implant debris both in vitro (using a human THP-1 macrophage cell line and primary human monocytes/macrophages) and in vivo. HIF-1α in peri-implant tissues of failed metal-on-metal implants were compared to similar tissues from people with metal-on-polymer hip arthroplasties, immunohistochemically. Increasing concentrations of cobalt ions significantly up-regulated HIF-1α with a maximal response at 0.3 mM. Cobalt-alloy particles (1 um-diameter, 10 particles/cell) induced significantly elevated HIF-1α, VEGF, TNF-α and ROS expression in human primary macrophages whereas Titanium-alloy particles did not. Elevated expression of HIF-1α was found in peri-implant tissues and synovial fluid of people with failing Metal-on-Metal hips (n = 5) compared to failed Metal-on-Polymer articulating hip arthroplasties (n = 10). This evidence suggests that Cobalt-alloy, more than other metal implant debris (e.g. Titanium alloy), can elicit hypoxia-like responses that if unchecked can lead to unusual peri-implant pathologies, such as lymphocyte infiltration, necrosis and excessive fibrous tissue growths.

Up-regulated expression of MIF by interfacial membrane fibroblasts and macrophages around aseptically loosened implants.

BACKGROUND: Local chronic inflammatory reaction plays an important role in the process of aseptic loosening of implants after total joint replacement. In addition, macrophage migration inhibitory factor (MIF) is a key upstream regulator of inflammation, and it is a significant regulator of inflammatory diseases. The purpose of this study is to investigate if the fibroblasts and macrophages in the interfacial membranes overexpress MIF. MATERIALS AND METHODS: The 15 tissue samples of interfacial membranes were obtained from the tissues around the aseptically loosened femoral implants adjacent to osteolytic lesion in 15 patients. The 15 control synovial samples of hip joints were obtained from 15 patients who underwent primary hip arthroplasty because of the fresh fracture of the femoral neck. The levels of MIF protein and mRNA were evaluated by ELISA assay, immunofluorescence labeling, and real-time RT-PCR. Fibroblasts and macrophages were identified by immunofluorescence labeling. RESULTS: The levels of MIF protein and mRNA were significantly increased, as well as the numbers of MIF+ fibroblasts and macrophages in the interfacial membranes compared with the control synovium. CONCLUSION: Not only the macrophages, but also the fibroblasts in interfacial membranes overexpress MIF. MIF may play a significant role in the process of aseptic-loosening implants after total joint replacement.

Autoimmunity and inflammation are independent of class II transactivator type PIV-dependent class II major histocompatibility complex expression in peripheral tissues during collagen-induced arthritis.

OBJECTIVE: To determine the regulation of class II major histocompatibility complex (MHC) expression in fibroblast-like synoviocytes (FLS) in order to investigate their role as nonprofessional antigen-presenting cells in collagen-induced arthritis (CIA). METHODS: Expression of class II MHC, class II MHC transactivator (CIITA), and Ciita isoforms PI, PIII, and PIV was examined by real-time quantitative polymerase chain reaction, immunohistochemistry, and flow cytometry in human synovial tissues, arthritic mouse joints, and human and murine FLS. CIA was induced in mice in which isoform PIV of Ciita was knocked out (PIV(-/-) ), in PIV(-/-) mice transgenic for CIITA in the thymus (K14 CIITA), and in their control littermates. RESULTS: HLA-DRA, total CIITA, and CIITA PIII messenger RNA levels were significantly increased in synovial tissue samples from patients with rheumatoid arthritis compared with the levels in tissue from patients with osteoarthritis. Human FLS expressed surface class II MHC via CIITA PIII and PIV, while class II MHC expression in murine FLS was entirely mediated by PIV. Mice with a targeted deletion of CIITA PIV lack CD4+ T cells and were protected against CIA. The expression of CIITA was restored in the thymus of PIV(-/-) K14 CIITA-transgenic mice, which had a normal CD4+ T cell repertoire and normal surface levels of class II MHC on professional antigen-presenting cells, but did not induce class II MHC on FLS. Synovial inflammation and immune responses against type II collagen were similar in PIV(-/-) K14 CIITA-transgenic mice and control mice with CIA, but bone erosion was significantly reduced in the absence of PIV. CONCLUSION: Overexpression of class II MHC is tightly correlated with CIITA expression in arthritic synovium and in FLS. Selective targeting of Ciita PIV in peripheral tissues abrogates class II MHC expression by murine FLS but does not protect against inflammation and autoimmune responses in CIA.

Do tissues from THA revision of highly crosslinked UHMWPE liners contain wear debris and associated inflammation?

BACKGROUND: Polyethylene wear debris is a major contributor to inflammation and the development of implant loosening, a leading cause of THA revisions. To reduce wear debris, highly crosslinked ultrahigh-molecular-weight polyethylene (UHMWPE) was introduced to improve wear properties of bearing surfaces. As highly crosslinked UHMWPE revision tissues are only now becoming available, it is possible to examine the presence and association of wear debris with inflammation in early implant loosening. QUESTIONS/PURPOSES: We asked: (1) Does the presence of UHMWPE wear debris in THA revision tissues correlate with innate and/or adaptive immune cell numbers? (2) Does the immune cell response differ between conventional and highly crosslinked UHMWPE cohorts? METHODS: We collected tissue samples from revision surgery of nine conventional and nine highly crosslinked UHMWPE liners. Polarized light microscopy was used to determine 0.5- to 2-µm UHMWPE particle number/mm2, and immunohistochemistry was performed to determine macrophage, T cell, and neutrophil number/mm2. RESULTS: For the conventional cohort, correlations were observed between wear debris and the magnitude of individual patient macrophage (ρ=0.70) and T cell responses (ρ=0.71) and between numbers of macrophages and T cells (ρ=0.77) in periprosthetic tissues. In comparison, the highly crosslinked UHMWPE cohort showed a correlation between wear debris and the magnitude of macrophage responses (ρ=0.57) and between macrophage and T cell numbers (ρ=0.68). Although macrophages and T cells were present in both cohorts, the highly crosslinked UHMWPE cohort had lower numbers, which may be associated with shorter implantation times. CONCLUSIONS: The presence of wear debris and inflammation in highly crosslinked UHMWPE revision tissues may contribute to early implant loosening.

Distinct immunohistomorphologic changes in periprosthetic hip tissues from historical and highly crosslinked UHMWPE implant retrievals.

Assessment of immune response to implant wear debris in periprosthetic tissue following total hip arthroplasty suggests that multiple factors are involved in the loss implant function. The current study investigated wear debris and the associated immunohistomorphologic changes in tissues from nine patients with historical (gamma air-sterilized) and nine highly crosslinked UHMWPE implant components. Paraffin embedded tissue sections were evaluated for the presence of histiocytes, giant cells, fibrocartilage/bone, and necrosis. To determine the incidence, degree and co-localization of immunohistomorphologic changes and wear, overlapping full-field tissue arrays were collected in brightfield and polarized light. The historical cohort tissues predominantly showed histiocytes associated with significant accumulations of small wear (0.5-2 microm), and giant cells associated with large wear (> or =2 microm). Frequently, focal regions of necrosis were observed in association with wear debris. For the highly crosslinked cohort, inflammation and associated wear debris were limited, but in tissues from patients revised after implantation times of >2 years a response was observed. Whereas significant amounts of fibrocartilage/bone were observed in patients at earlier implantation times. In both cohorts, tissue responses were more extensive in the retroacetabular or proximal femoral regions. The current findings suggest that wear debris-induced inflammation may be a major contributor to the loss of implant function for both the historical and highly crosslinked cohorts, but it is not the primary cause of early implant loosening. This study highlights the importance of using a more quantitative and standardized assessment of immunohistomorphologic responses in periprosthetic tissues, and emphasizes differences in specific anatomical regions of individual patient tissues.

Early failure of metal-on-metal bearings in hip resurfacing and large-diameter total hip replacement: A consequence of excess wear.

Early failure associated with adverse reactions to metal debris is an emerging problem after hip resurfacing but the exact mechanism is unclear. We analysed our entire series of 660 metal-on-metal resurfacings (Articular Surface Replacement (ASR) and Birmingham Hip Resurfacing (BHR)) and large-bearing ASR total hip replacements, to establish associations with metal debris-related failures. Clinical and radiological outcomes, metal ion levels, explant studies and lymphocyte transformation tests were performed. A total of 17 patients (3.4%) were identified (all ASR bearings) with adverse reactions to metal debris, for which revision was required. This group had significantly smaller components, significantly higher acetabular component anteversion, and significantly higher whole concentrations of blood and joint chromium and cobalt ions than asymptomatic patients did (all p < 0.001). Post-revision lymphocyte transformation tests on this group showed no reactivity to chromium or cobalt ions. Explants from these revisions had greater surface wear than retrievals for uncomplicated fractures. The absence of adverse reactions to metal debris in patients with well-positioned implants usually implies high component wear. Surgeons must consider implant design, expected component size and acetabular component positioning in order to reduce early failures when performing large-bearing metal-on-metal hip resurfacing and replacement.

Toll-like receptors and aseptic loosening of hip endoprosthesis-a potential to respond against danger signals?

Bacterial remnants and subclinical biofilms residing on prosthesis surfaces have been speculated to play a role in hip implant loosening by opsonizing otherwise relatively inert wear particles. The innate immune system recognizes these microbial pathogen-associated molecular patterns (PAMPs) using Toll-like receptors (TLRs). Our objective was to evaluate the possible presence of TLRs in aseptic synovial membrane-like interface tissue. Bacterial culture-negative, aseptic (n = 4) periprosthetic synovial membrane-like tissue was compared to osteoarthritis synovial membrane (n = 5) for the presence of cells positive for all known human functional TLRs, stained using specific antibodies by immunohistochemistry, and evaluated using morphometry. In comparison to osteoarthtritic synovium, the number of TLR-positive cells was found to be increased in the aseptic setting, reflecting the considerable macrophage infiltration to the tissues investigated. Thus aseptic periprosthetic tissue seems to be very reactive to PAMPs. It has been recently recognized that TLR do not only respond to traditional PAMPs, but also to endogenous alarmings or danger signals released from necrotic and activated cells. Alarming-TLR interaction in the periprosthetic tissue might be a novel mechanism of aseptic loosening of endoprosthesis.

Lymphocyte proliferation responses in patients with pseudotumors following metal-on-metal hip resurfacing arthroplasty.

Locally destructive soft tissue pseudotumor has been reported in patients following metal-on-metal hip resurfacing arthroplasty (MoMHRA). A delayed hypersensitivity reaction type IV to nickel (Ni), chromium (Cr), or cobalt (Co) has been suggested to play a role in its aetiology. The aim of this study was to investigate the incidence and level of metal-induced systemic hypersensitivity in patients with MoMHRA, both with and without pseudotumor by measuring lymphocyte proliferation responses to metals. A total of 92 patients were investigated: (1) MoMHRA patients with pseudotumors (nine female, one male); (2) MoMHRA patients without pseudotumors (30 female, 30 male); and (3) age-matched control subjects without metal implants (9 female, 13 male). The venous blood samples were collected for serum Ni, Co, and Cr ion level measurements and lymphocyte transformation tests (LTT). A higher incidence and level of enhanced lymphocyte reactivity only to Ni was found in patients with MoMHRA compared to the patients without MoM implants, reflecting exposure and immune reactivity. However, lymphocyte reactivity to Co, Cr, and Ni did not significantly differ in patients with pseudotumors compared to those patients without pseudotumors. This suggests that systemic hypersensitivity type IV reactions, as measured by lymphocyte proliferation response to these metals, may not be the dominant biological reaction involved in the occurrence of the soft tissue pseudotumors.

Immune responses in patients with metal-on-metal hip articulations: a long-term follow-up.

Metal-on-metal (MoM) hip bearings are being inserted into ever-younger patients. The effects on the immune system of chronic exposure are unknown. We investigated the immune response of patients with MoM hip bearings. In patients with MoM implants, the expression of antigen-presenting cell (APC) surface molecules (CD86 and HLA-DR) was seen to be significantly higher (P < .05) than control group. High levels of APC surface molecules suggest an activated state and attempts to propagate an immune response. However, in the same group, the expression of T-cell markers (CD3 and CD28) was low, indicating a small T-cell population. This suggests, despite the activation of APCs, that T cells down-regulate immune responses in MoM articulations. Conversely, in metal-on-polyethylene articulations, expression of T-cell molecules was elevated and expression of APC molecules lowered.

[Inflammatory reactions in the wear particle induced and infectious periprosthetic membrane of loosened hip- and knee endoprostheses: pathogenetic relevance of differentially expressed genes cd9, cd11b, cd18, cd52 and pdgfrbeta]. / Inflammatorische Reaktion bei abriebinduzierter und infektiöser Lockerung von Hüft- und Knieendoprothesen.

BACKGROUND: A previous cDNA-microarray analysis described constantly differentially expressed genes in wear particle induced and infectious SLIM (synovial-like interface membrane). This study aims to validate the cDNA microarray data in order to approve differences of the gene expression profiles of RNA and proteins. METHODS: Tissue from 16 wear particle induced and 20 infectious periprosthetic membranes were analyzed by RT-PCR and immunohistology with regard to the expression of inflammatoric associated genes. RESULTS: RT-PCR showed the genes cd9, cd11b, cd18, cd52 as well as pdgfrbeta in interface membranes. In the wear particle induced membrane the immunohistochemical analysis showed a significantly weaker gene expression of PDGFRbeta, whereas the differential overexpression of CD9, CD11b and CD52 was confirmed. For CD18, there was no difference in expression between wear induced and infectious periprosthetic tissue. CONCLUSION: Different pathomechanisms, which are reflected by different gene expression profiles, might produce different types of periprosthetic membranes. By RT-PCR and immunohistochemical analysis the micro array data of the genes cd9, cd11b, cd52 and pdgfrbeta could be validated. Identifying the gene products of cd9, cd11b and cd52 in blood or tissue may help to differentiate between wear induced and infectious loosening.

Co-stimulatory and adhesion molecules of dendritic cells in rheumatoid arthritis.

Dendritic cells (DCs) in the rheumatoid arthritis (RA) joint mediate the immunopathological process and act as a potent antigen presenting cell. We compared the expression of co-stimulatory and adhesion molecules on DCs in RA patients versus controls with traumatic joint lesions and evaluated the correlation between the immunophenotypical presentation of DCs and the clinical status of the disease. Samples of peripheral venous blood, synovial fluid (SF) and synovial tissue (ST) were obtained from 10 patients with RA at the time of hip or knee replacement and from 9 control patients with knee arthroscopy for traumatic lesions. Clinical status was appreciated using the DAS28 score. Blood, SF and dissociated ST cell populations were separated by centrifugation and analyzed by flow cytometry. Cells phenotypes were identified using three-color flow cytometry analysis for the following receptors HLA-DR, CD80, CD83, CD86, CD11c, CD18, CD54, CD58, CD3, CD4, CD8, CD19, CD20, CD14, CD16, CD56. HLA-DR molecules, co-stimulatory receptors CD80, CD86, CD83 and adhesion molecules CD18, CD11c, CD54, CD58, were analyzed by two-color immunofluorescence microscopy on ST serial sections. In patients with active RA (DAS28>5.1) we found a highly differentiated subpopulation of DCs in the ST and SF that expressed an activated phenotype (HLA-DR, CD86+, CD80+, CD83+, CD11c+, CD54+, CD58+). No differences were found between circulating DCs from RA patients and control patients. Our data suggest an interrelationship between clinical outcome and the immunophenotypical presentation of DCs. Clinical active RA (DAS28>5.1) is associated with high incidence of activated DCs population in the ST and SF as demonstrated by expression of adhesion and co-stimulatory molecules.

[The immunological aspects of a hip joint lesion in childhood]. / Immunologicheskie aspekty porazheniia tazobedrennogo sostava v detskom vozraste.

The paper presents an in-depth analysis of immunological mechanisms of the hip joint synovitis development in children. Studied in the pediatric patients with transient coxitis, Perthes disease, and tuberculous coxitis (n = 54, 15, and 15 respectively) with the aid of flow cytofluorometer FACStar PLUS was the subpopulation of immunocompetent cells with a wide spectrum of MCAB. Controls (n = 35) were sex and age-matched. Comparative analysis of immunological parameters in the above children disclosed a toxic-and-allergic origination of transient synovitis with predominant affection of the T-cell link of immunity (T-helpers failure and activation of T-suppressors). Joint mucose injury was noted to be developing against the background of reduction of serum IgA. Activation of non-specific mechanisms (natural killers, increase in SDH activity) is of compensatory character. Mechanisms of activation of cell processes (expression of panmitogenic receptor CD4+ antigen) in Perthes disease warrant further studies. In patients with tuberculous coxitis, immunological incompetence develops in the presence of cytotoxic reactions and activation of the B-link, with the production of IgM being on the increase but with no essential changes in the IgG fraction. It is necessary that selective stimulators of T-helpers be included into the treatment scheme together with drugs capable of exerting a selective effect on the T-link of immunity.

Knee and/or hip joint destruction in rheumatoid arthritis is associated with HLA-DRB1*0405 in Japanese patients.

To determine the prognostic factors for knee and/or hip joint destruction in rheumatoid arthritis (RA) patients, we typed 379 RA patients for HLA-DRB alleles and analysed the antigen frequencies. The DRB1*0405 antigen frequency in RA patients who underwent total knee replacement and/or total hip replacement was significantly higher than in those who did not have replacements, which meant that DRB1*0405 was associated with knee and/or hip joint destruction. This finding may be of value for predicting knee and/or hip joint destruction in RA.