Rheumatoid Arthritis: Pers JO

Devauchelle-Pensec V, Pers JO, Youinou P, Saraux A. · No affiliation provided · Rev Med Interne. · Pubmed #18403066 No free full text.

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Youinou P, Daridon C, Saraux A, Devauchelle V, Pers JO. · No affiliation provided · Clin Exp Rheumatol. · Pubmed #17181915 No free full text.

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Youinou P, Pers JO, Saraux A, Pennec YL. · No affiliation provided · Clin Exp Immunol. · Pubmed #15958065 links to  free full text

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Pers JO, Le Pottier L, Devauchelle V, Saraux A, Youinou P. · Laboratoire d'immunologie, centre hospitalier universitaire de Brest, B.P. 824, 29609 Brest, France. · Rev Med Interne. · Pubmed #18403061 No free full text.

Abstract: INTRODUCTION: Sjögren's syndrome (SS) is an autoimmune epithelitis hallmarked by a disruption of epithelial cells, the subsequent lymphocytic infiltration of lachrymal and salivary glands (SGs), and their ensuing dryness. One may posit that SS is triggered by viruses, and/or modulated by sex steroid hormones, and there is indeed a consensus that its aetiology is multifactorial, with genetic factors interacting with environmental agents. CURRENT KNOWLEDGE AND KEY POINTS: T-cells have long occupied central stage of the debate on the type of lymphocytes involved in the pathogenesis of SS. The relevance of B cells has, however, been emphasized over the past five years and new insights into their functions revealed. Furthermore, increased levels of the B-cell activating factor (BAFF) may be responsible for quantitative and qualitative anomalies of B-cells found in SS such as emergence of self reactive B-cells. This review reports compelling evidence that B-cells are involved in the pathophysiology of SS. PROSPECTS: Since SS may thus be conceived as a model for B-cell-induced autoimmunity, it is no surprise that B-cell ablative-treatment has proven to be relatively effective in SS.

Youinou P, Devauchelle V, Hutin P, Le Berre R, Saraux A, Pers JO. · Department of Immunopathology, Brest University Medical School, Brest, France. · Clin Rev Allergy Immunol. · Pubmed #17992590 No free full text.

Abstract: Although the relative contributions of T cells and B cells in Sjögren's syndrome (SS) are far from being settled, recent studies have suggested a crucial role for B cells in its pathophysiology. Early investigations have focused on the ability of B cells to produce autoantibodies, and new studies have enlarged the range of their functions. For example, beyond the paradigm that T lymphocytes maintain strict control over B cells, the latter cells are now acknowledged to solicit their own help from the former cells and release a flurry of cytokines. Further, some of these B cells act as antigen-presenting cells. Increased levels of the B cell activating factor (BAFF) found in SS may be responsible for high numbers of circulating Bm2/Bm2' cells and associated functional abnormalities of B cells, such as a BAFF-induced increased expression of CD19, which decreases the required strength generated by antigen binding for transmitting its signal. This review reports compelling evidence that B cells are involved in the pathophysiology of SS. As this brings novel prospects for the treatment of the disease, it is no surprise that B cell ablative treatment has proven to be relatively efficacious in SS.

Daridon C, Guerrier T, Devauchelle V, Saraux A, Pers JO, Youinou P. · Laboratory of Immunology, Brest University Medical School Hospital, Brest, France. · Autoimmun Rev. · Pubmed #17643928 No free full text.

Abstract: Analysis of salivary glands of patients with primary Sjögren's syndrome has yielded conflicting results with respect to T helper (Th)1/Th2 polarization. This balance might parallel the progress of the local lesions. B-cells are now taking center stage in this disease. They can also be primed to differentiate into two cytokine-production pathways, dubbed B effector (Be) 1 and Be2 cells. This is discussed in the light of our recent finding that Be1 accompany Th1, while Be2 accompany in the tissue lesions.

Bosello S, Pers JO, Rochas C, Devauchelle V, De Santis M, Daridon C, Saraux A, Ferraccioli GF, Youinou P. · Laboratory of Immunology, Medical School, Brest, France. · Int J Immunopathol Pharmacol. · Pubmed #17346422 No free full text.

Abstract: Interest in B-cells has been revived due to the description of new functions. Supporting a role for B-cells in the genesis of autoimmune diseases is the fact that the B-cell activating factor of the TNF ligand family (BAFF) is essential in their physiology. However, in each disease, this is restricted to a subgroup of patients. Based on experiments in mice, and validated in humans, this new cytokine has been highlighted. Excessive production of BAFF alters immune tolerance by rescuing self-binding B-cells. Overexpression in mice leads to autoimmune manifestation, and BAFF levels are elevated in the serum of autoimmune patients. Similar abnormalities occur in chronic lymphocytic leukemia. Recent works suggest that antagonizing the protein (or competing for its receptors) is relevant to the treatment. Advances in our understanding of the BAFF system offers the opportunity to improve our therapeutic approach.

Pers JO, Jamin C, Predine-Hug F, Lydyard P, Youinou P. · Division of Dentistry, Brest University Medical School Hospital, Brest, France. · Int J Mol Med. · Pubmed #10028047 No free full text.

Abstract: The CD5(+) B cell population is prominent in early life and produce low avidity and, thereby, polyreactive antibodies. CD5(+) B cells are receptive to cytokines and interleukin-10 seems to be influential in the regulation of some of these CD5(+) B cells. The question of whether CD5 is a marker of activation or a molecule specific for a B cell lineage remains unresolved because evidence in support or against a separate lineage are still a matter for debate. However, we suggest the possibility of different kind of CD5(+) B cells. Indeed, activated CD5(+) B cells do proliferate, following CD5 engagement, while resting CD5(+) B cells do not. Moreover, three ligands for CD5 have, thus far, been identified but their functional effects are yet unknown. CD5(+) B cells probably play a role in setting up the idiotype network, antigen presentation and tolerance induction. B cells of most of the chronic lymphoid leukemias express CD5 molecules and, surprisingly, these cells may be expanded in non-organ-specific autoimmune diseases, such as rheumatoid arthritis or primary Sjögren's syndrome. CD5(+) B cells seems to be involved in the autoantibody production (this does not necessarily imply that pathogenic autoantibodies are produced by CD5(+) B cells) in autoimmune disease and particularly susceptible to transformation in lymphoproliferative disorders. Thus, this B cell population appears to play a key role at the crossroad of the non-organ-specific autoimmune diseases and B lymphoproliferative disorders.

Devauchelle-Pensec V, Pennec Y, Morvan J, Pers JO, Daridon C, Jousse-Joulin S, Roudaut A, Jamin C, Renaudineau Y, Roué IQ, Cochener B, Youinou P, Saraux A. · Hôpital de la Cavale Blanche, CHU Brest, France. · Arthritis Rheum. · Pubmed #17330280 links to  free full text

Abstract: OBJECTIVE: There is evidence to support a dominant role for B cells in the pathophysiology of primary Sjögren's syndrome (SS). Therefore, we evaluated the safety and efficacy of anti-CD20 monoclonal antibody. METHODS: Sixteen patients who met the new American-European Consensus Group criteria for primary SS and scored >50 on at least 2 of 4 visual analog scales (VAS; 100 mm) evaluating global disease, pain, fatigue, and global dryness received infusions of low-dose rituximab (375 mg/m(2)) at weeks 0 and 1 without steroid premedication. RESULTS: Slow rituximab infusions (100 mg/hour) were well tolerated, with only 1 patient experiencing serum sickness-like disease. There was a dramatic reduction in B cells of the blood and salivary gland (SG). At week 12, VAS scores with respect to fatigue and dryness (P < 0.05), tender point count (P < 0.035), and quality of life as evaluated by the Short Form 36 questionnaire (SF-36; P < 0.001) were significantly improved. At week 36, significant improvements were noted in the 4 VAS scores (P < 0.05), tender joint count (P = 0.017), tender point count (P = 0.027), and SF-36 (P < 0.03). Pulmonary manifestations were ameliorated in 1 patient. Patients with improvements on at least 3 of the 4 VAS scores at any visit (n = 11) had a shorter disease duration than the other patients (n = 5; mean +/- SD duration 3.8 +/- 5.4 versus 30.1 +/- 29.5 years; P = 0.02). CONCLUSION: Low-dose rituximab infusions were well tolerated without the benefit of steroids. Infusions induced a rapid depletion of B cells in the blood and SG and could improve primary SS. Controlled studies are needed.

Le Pottier L, Devauchelle V, Fautrel A, Daridon C, Saraux A, Youinou P, Pers JO. · Equipe d'Accueil 2216 and Institut Fédératif de Recherche 418, Science et Ingénierie en Biologie-Santé, Université de Brest, Brest, and Université Européenne de Bretagne, Brest, France. · J Immunol. · Pubmed #19265132 No free full text.

Abstract: This study reports on the characterization of B cells of germinal center (GC)-like structures infiltrating the salivary glands (SGs) of patients with Sjögren's syndrome. Eight two-color combinations were devised to characterize the phenotype of these B cells in 11 SG specimens selected from biopsies obtained from 40 Sjögren's syndrome patients and three normal tonsils. The 9G4 mAb, which recognizes V4.34-encoded autoAbs, enabled us to identify autoreactive B cells. Quantitative RT-PCR was used to determine the level of mRNAs for activation-induced cytidine deaminase (AICDA), repressors and transcription factors. CD20(+)IgD(-)CD38(+)CD21(+)CD24(-) B cells, similar to those identified in tonsil GCs, were seen in the SGs of four patients and, and since they expressed AICDA, they were termed "real GCs". CD20(+)IgD(+)CD38(-)CD21(+)CD24(+) B cells, seen in aggregates from the remaining seven samples, were characteristically type 2 transitional B cells and marginal zone-type B cells. They lacked AICDA mRNAs and were termed "aggregates". Real GCs from SGs contained mRNAs for Pax-5 and Bcl-6, like tonsil GC cells, whereas aggregates contained mRNAs for Notch-2, Blimp-1, IRF-4, and BR3, similar to marginal zone B cells. Further experimental data in support of this dichotomy included the restriction of CXCR5 expression to real GC cells, while sphingosine 1-phosphate receptor 1 was expressed only in aggregates. In contrast, both types of B cell clusters expressed the idiotype recognized by the 9G4 mAb. Our data indicate that, in SGs, a minority of B cell clusters represent genuine GC cells, while the majority manifest features of being type 2 transitional B cells and marginal zone cells. Interestingly, both types of B cell aggregates include autoreactive B cells.

Pers JO, Saraux A, Pierre R, Youinou P. · Department of Dentistry, Brest University Medical and Dental School, Brest, France. · J Periodontol. · Pubmed #18771364 No free full text.

Abstract: BACKGROUND: Because periodontitis presents many similarities with rheumatoid arthritis (RA) with regard to tumor necrosis factor-alpha (TNF-alpha)-induced bone resorption, the benefits of TNF-alpha blockade in RA prompted us to determine its efficacy in treating coexisting periodontitis. METHODS: Periodontal status was evaluated in 40 subjects with RA who were divided into two groups: Group I contained 20 subjects who had received infliximab every 6 weeks for > or =22 months at the time of periodontal evaluation. The 20 subjects in group II were evaluated before their first infusion with infliximab. Nine subjects in group II had periodontitis. These subjects were reevaluated after they received nine infusions of infliximab. RESULTS: Infliximab tended to aggravate gingival inflammation as indicated by differences in the modified gingival and papillary bleeding indices between subjects in groups I and II with coexisting periodontitis before and after treatment. Methotrexate had no effect on periodontal status. Although the plaque index revealed that bacterial infection persisted, the probing depth was equal in groups I and II and equivalent before and after treatment in subjects with periodontitis, whereas attachment loss was decreased after infliximab treatment. CONCLUSIONS: Inflammation and destruction constitute two interrelated yet separate components of periodontitis in patients with RA. Therefore, TNF-alpha blockade could be beneficial in the treatment of periodontitis.

Pers JO, Daridon C, Bendaoud B, Devauchelle V, Berthou C, Saraux A, Youinou P. · Department of Immunopathology, Brest University Medical School, Brest, France. · Clin Rev Allergy Immunol. · Pubmed #18270858 No free full text.

Abstract: Although T-lymphocytes have long been regarded as the prime effector of autoimmune diseases, numerous studies have since highlighted a key role for B-lymphocytes. For example, disturbances in the distribution of circulating B-cell subsets were reported in primary Sjögren's syndrome (pSS) and systemic lupus erythematosus (SLE). Consequently, this was the rationale to treat such patients for B-cell depletion with anti-CD20 monoclonal antibody (rituximab). The aim of this review is to describe and analyze the B-cell subset distribution at baseline and after rituximab therapy in patients with SLE, rheumatoid arthritis, and pSS. Finally, we will compare factors that may interfere with anti-CD20-mediated B-cell depletion in these autoimmune diseases.

Pers JO, Devauchelle V, Daridon C, Bendaoud B, Le Berre R, Bordron A, Hutin P, Renaudineau Y, Dueymes M, Loisel S, Berthou C, Saraux A, Youinou P. · Brest University Medical School, Brest, France. · Arthritis Rheum. · Pubmed #17469105 links to  free full text

Abstract: OBJECTIVE: Treatment with rituximab depletes B cells from the peripheral blood (PB) and salivary glands (SGs) of patients with primary Sjögren's syndrome (SS). The purpose of this study was to track the repopulation of B cell subsets in PB as well as their subsequent homing into SGs in patients with primary SS treated with rituximab. METHODS: A series of 4-color flow cytometry experiments delineated B cell subsets in 15 patients with primary SS. All were tested on days 8 and 15 of treatment. Nine of the patients were followed up monthly for 10 months, and the remaining 6 patients were followed up monthly for 24 months. Enzyme-linked immunosorbent assays were developed to measure serum levels of BAFF and rituximab. SGs were biopsied at the start of the study and 4 months after treatment in 15 patients, 12 months after treatment in 3 patients, and 24 months after treatment in 2 patients. RESULTS: Baseline serum levels of BAFF correlated inversely (r = -0.92, P < 5 x 10(-4)) with the duration of B cell depletion: the higher the BAFF levels, the shorter the duration of B cell depletion. Four B cell subsets repopulated the PB: plasmablasts (CD19+, CD5-,IgD-,CD38++), transitional type 1 (T1) B cells (CD19+,CD5+,IgD+,CD38++), mature Bm2 cells (CD19+,CD5+/-,IgD+,CD38+/-), and memory B cells (CD19+,CD5-,IgD-,CD38-). Increased numbers of Bm2 cells and decreased memory B cells reappeared with time. Sequential SG biopsies revealed that B cells were absent in these glands for 12 months: they were detected 24 months after rituximab treatment. Memory and T1 B cells were the first B cells identified locally. CONCLUSION: The timing of B cell repopulation is modulated by BAFF and is followed by reconstitution of the preexisting abnormalities.

Daridon C, Devauchelle V, Hutin P, Le Berre R, Martins-Carvalho C, Bendaoud B, Dueymes M, Saraux A, Youinou P, Pers JO. · Laboratory of Immunology, Brest University Medical School Hospital, Brest, France. · Arthritis Rheum. · Pubmed #17393395 links to  free full text

Abstract: OBJECTIVE: To identify the cells that produce BAFF in the salivary glands of patients with primary Sjögren's syndrome (SS), and to analyze BAFF receptor expression by local T and B lymphocytes. METHODS: We used 3 methods to identify the source of BAFF: in situ hybridization of the transcripts for BAFF combined with staining of membrane markers, regular and real-time reverse transcription-polymerase chain reaction (RT-PCR) of cultured epithelial cells, and RT-PCR of sorted single-cell T and B lymphocytes eluted from salivary glands. Cells expressing TACI, BCMA, and B lymphocyte stimulator receptor 3 (BR-3) were disclosed by combining each specific staining of the receptors with each specific staining of the cells. The function of BAFF generated by epithelial cells on B lymphocytes was determined in short-term cocultures. RESULTS: Transcripts for BAFF were seen in epithelial cells and infiltrating T lymphocytes and, for the first time, were detected in local B cells. It is interesting that BR-3 was present on these B cells but not on T cells. In contrast, TACI and, to a lesser degree, BCMA were observed on transitional B lymphocytes, whereas T lymphocytes were devoid of receptors for BAFF. Furthermore, this cytokine was shown to be functional, in that epithelial cell-bound BAFF extended the survival of normal B cells, but cell-free BAFF released in the supernatants did not. CONCLUSION: These experiments establish that in primary SS, BAFF is produced not only by epithelial cells and T cells but also by B cells. The expression of receptors for BAFF would thus allow these receptors to participate in an autocrine pattern of self-stimulation.

Le Pottier L, Devauchelle V, Pers JO, Jamin C, Youinou P. · Brest University Medical School, Brest, France. · Autoimmun Rev. · Pubmed #17289550 No free full text.

Abstract: Major breakthroughs have occurred with classification of B-cells into populations and subpopulations. With respect to their expression of CD5, they comprise the B1 and B2 populations, with the former further divided into B1a and B1b subpopulations. The oncologic process starts from transitional type 1 (T1) and T2 immature B-cells, through marginal zone or germinal center B-cells, ending up with memory B-cells and plasma cells (PCs). They may also be categorized based on their functional commitment with polarized B effector (Be)1 and Be2, with B-activating factor of the tumor-necrosis factor-producing B-cells, and with short-lived and long-lived PCs. Such a seemingly homogeneous family of cells has thus turned out to be a genuine mosaic of B-lymphocyte subsets.

Daridon C, Pers JO, Devauchelle V, Martins-Carvalho C, Hutin P, Pennec YL, Saraux A, Youinou P. · Laboratory of Immunology, Brest University Medical School Hospital, BP824, F-29609 Brest, France. · Arthritis Rheum. · Pubmed #16802367 links to  free full text

Abstract: OBJECTIVE: To identify B cell subpopulations participating in the lymphocyte infiltrate of salivary glands from patients with primary Sjögren's syndrome. A special emphasis was placed on those B lymphocytes included in the ectopic germinal centers (GCs). METHODS: The presence of B cells in salivary glands and their polyclonality were ascertained by phenotyping and reverse transcription-polymerase chain reaction in salivary gland samples from 18 patients. Their phenotype was thoroughly analyzed using a number of double-staining combinations. The results obtained in tissue sections were confirmed by fluorescence-activated cell sorting analysis of B cells eluted from salivary glands, and these findings were compared with those in tonsils. RESULTS: Memory-type B cells were defined as CD20+, CD27+ and were seen in all specimens, whereas GCs were found in only 7 specimens. Furthermore, B cells found in these GCs lacked certain characteristics of centroblasts and centrocytes. Instead, they fulfilled the criteria for transitional type II (TII) B cells and resembled marginal-zone B cells. BAFF (the assistance of which is required for proper transformation of transitional TI B cells into transitional TII B cells) accumulated adjacent to transitional and marginal-zone-like B lymphocytes. Further evidence for the involvement of BAFF came from the expression of its receptors on infiltrating B cells. CONCLUSION: These transitional TII and marginal-zone-like B cells are probably instrumental in the local production of autoantibodies and possibly influential in the ensuing destruction of epithelial cells.

d'Arbonneau F, Pers JO, Devauchelle V, Pennec Y, Saraux A, Youinou P. · Immunology Laboratory, Brest University Medical School, F-29609 Brest, France. · Arthritis Rheum. · Pubmed #16385503 links to  free full text

Abstract: OBJECTIVE: To determine the effect of excessive production of BAFF on the distribution and function of B cell subsets in patients with primary Sjögren's syndrome (SS). METHODS: The phenotype of B lymphocytes was analyzed by flow cytometry. Differences in the expression level of membrane IgD and CD38 were used to identify B lymphocyte subsets evolving from naive Bm1 through memory Bm5 cells. Based on our finding of a low expression of CD45RA, we sorted Bm2/Bm2' cells to determine the time course of translocation of the CD19 molecule and the B cell receptor into lipid rafts, by confocal microscopy. Serum levels of BAFF were measured by an enzyme-linked immunosorbent assay developed in-house. RESULTS: "Circulating" Bm2/Bm2' cells were expanded in patients with primary SS compared with rheumatic disease controls and with normal controls. In addition, these B cell subsets were functionally abnormal. Prolonged residency of the B cell receptor in lipid rafts in these cells was associated with elevated CD19 expression in B cells, most notably, Bm2 and Bm2' cells, obtained from the patients with primary SS. BAFF levels were higher in the patients than in the normal controls and correlated with the percentage of Bm2/Bm2' cells and their expression of CD19 in primary SS patients. These correlations were confirmed by placing sorted Bm1 or Bm2 cells from normal controls in culture in the presence or absence of BAFF. CONCLUSION: Bm2/Bm2' cells express more CD19 molecules in primary SS patients than in normal controls. BAFF might participate in this elevated expression of CD19. These patients might be suitable candidates for treatment with BAFF antagonists.

Pers JO, d'Arbonneau F, Devauchelle-Pensec V, Saraux A, Pennec YL, Youinou P. · Brest University Medical School, France. · Arthritis Rheum. · Pubmed #16052575 links to  free full text

Abstract: OBJECTIVE: To correlate the periodontal status of 15 patients with primary Sjögren's syndrome (SS) with their salivary levels of BAFF. METHODS: The periodontal status of 15 patients who fulfilled the criteria for primary SS was compared with that of 15 controls with xerostomia who did not fulfill the criteria for primary SS but had similar symptoms of dry mouth. The level of BAFF was measured in paired samples of saliva and serum using in-house enzyme-linked immunosorbent assays. Periodontitis was assessed by the plaque index, the modified gingival index, the papillary bleeding index, and the periodontal pocket depth. RESULTS: Notwithstanding the better oral hygiene practices of the patients with primary SS compared with those of the xerostomia controls and the subsequent reduction of their plaque index scores, complications of periodontitis, such as bleeding, gingival hypertrophy, and periodontal pockets, were not improved. This failure to ameliorate the complications of periodontitis in patients with primary SS was associated with high levels of BAFF in their saliva compared with the levels in xerostomia controls (7.4 +/- 2.1 versus 1.0 +/- 0.4 ng/ml [P < 0.002]). The levels of BAFF in saliva did not correlate with the levels in sera but did correlate with the periodontal pocket depth (P < 0.002). CONCLUSION: These findings are similar to the bone resorption observed in patients with rheumatoid arthritis. They suggest that the known effect of B cells in periodontitis would be partly mediated by salivary BAFF in patients with primary SS.

Pers JO, Daridon C, Devauchelle V, Jousse S, Saraux A, Jamin C, Youinou P. · Department of Immunology, Brest University Medical School Hospital, BP824, F29609, Brest, France. · Ann N Y Acad Sci. · Pubmed #16014518 No free full text.

Abstract: The B-cell activity factor (BAFF) acts as a positive regulator of B-cell function. To gain further insight into the understanding of B-cell hyperactivity in autoimmune diseases, the serum level of BAFF was determined in 43 systemic lupus erythematosus (SLE) patients, 58 primary Sjögren's syndrome (pSS) patients, 28 rheumatoid arthritis (RA) patients, and 68 normal control subjects using an in-house sandwich ELISA. A commercial kit was used to detect soluble CD23 (sCD23) reflecting B-cell activation. In-house assays for the detection of autoantibodies also were used. We found an increased level of BAFF in SLE, pSS, and RA sera compared with normal subjects (respectively, 10.6 +/- 8.5, 15.8 +/- 12.9, 9.7 +/- 1.5 ng/mL vs. 4.6 +/- 2.9 ng/mL, P < .001). sCD23 released on B-cell activation also was found to be elevated in SLE, pSS, and RA compared with normal sera. However, no correlation was found between the circulating BAFF and the level of sCD23. By contrast, we observed that high levels of BAFF were associated with the presence of autoantibodies (anti-double-stranded DNA antibodies in SLE, anti-SSA antibodies in pSS, and rheumatoid factors in RA). Our data suggest that BAFF is influential in driving antibody production rather than activation of the B lymphocytes in autoimmune diseases.

Durand V, Pers JO, Renaudineau Y, Saraux A, Youinou P, Jamin C. · Laboratory of Immunology, Institut de Synergie des Sciences et de la Santé, Brest University Medical School, France. · J Leukoc Biol. · Pubmed #11272273 links to  free full text

Abstract: Anti-Fc gamma receptor IIIb (Fc gammaRIIIb) human autoantibodies (Ab) have been classified previously into three groups, based on the results of an indirect immunofluorescence (IIF) test and an enzyme-linked immunosorbent assay (ELISA): IIF+/ELISA+ (group A), IIF+/ELISA- (group B), and IIF-/ELISA+ (group C) sera. In this study, differential effects between IIF+ autoAb, recognizing cell-bound Fc gammaR, and those ELISA+, recognizing only cell-free Fc gammaR, were studied on polymorphonuclear neutrophils (PMN). Neither group A nor B autoAb was cytotoxic, although both prolonged the survival of PMN by delaying spontaneous apoptosis. By the same extent, the PMN-binding antisera stimulated the appearance of a CD11b(dim) population, following a 12-h incubation. This event was associated with a lowered expression of beta2 integrin molecules, resulting in altered PMN function. Treatment with groups A and B autoAb reduced adhesiveness and respiratory burst. This impairment of the responses was more pronounced when the cells originated from donors NA1+ NA1+ rather than donors NA2+ NA2+. From our observations, the influences of anti-Fc gammaRIIIb autoAb on PMN survival, as well as function and subsequent dysregulation of the inflammatory response, have proven somewhat dependent on their target antigens, as determined by IIF coupled with ELISA and Fc gammaRIIIb polymorphism.