Les neutropénies auto-immunes (NAI) sont primitives ou secondaires, principalement associées à des maladies auto-immunes, des hémopathies, et plus rarement aux déficits immunitaires primitifs ou à certains médicaments ou infections. Les NAI primitives, bénignes et transitoires, sont plus souvent observées chez le petit enfant. Les NAI secondaires sont l’apanage de l’adulte. Elles font discuter les autres causes de neutropénies, non immunes. Dans cette revue générale, nous rappelons les principales étiologies des NAI, leur diagnostic différentiel, les différentes méthodes du diagnostic biologique et les modalités de la prise en charge thérapeutique.

Autoimmune neutropenias (AIN) are classically divided into primary AIN and secondary AIN. The latter are associated with autoimmune disorders, hematologic malignancies, primary immune deficiencies, drug exposure or infections. In this review we will focus on the major aetiologies of AIN, their differential diagnosis, the various methods in biological diagnosis, and the treatment.

We determined the frequency of post-transfusion alloimmunisation against platelet and granulocyte antigens in 51 Tunisian polytransfused patients with haematological diseases. Serum samples were analysed by a standard and an antiglobulin-augmented lymphocytotoxicity technique, a granulocyte agglutination test, a granulocyte immunofluorescence test, a platelet immunofluorescence test and the monoclonal antibody-specific immobilisation of platelet antigens assay. No granulocyte-specific antibodies were detected. HLA antibodies were found in 58.8% of patients. Platelet-specific antibodies were detected in four patients and were directed against human platelet antigen (HPA)-5b, HPA-1b and HPA-3a. The three patients with Glanzmann's thrombasthenia developed anti-GPIIb/IIIa antibodies. This study provides immunogenetic information that could improve the management of transfusion therapy in Tunisia.

To characterize the antigenic targets of anti-platelet antibodies (APA) found in systemic lupus erythematosus (SLE)-associated thrombocytopenia, 48 patients with immune thrombocytopenia and SLE were compared with 20 patients with SLE who had never been thrombocytopenic. Both cases and controls were tested for circulating APA by an indirect platelet suspension immunofluorescence assay (PSIIFT) and by indirect monoclonal antibody specific immobilization of platelet antigens (MAIPA). A direct platelet suspension immunofluorescence assay (PSIFT) was also used for antibodies bound to platelets in vivo in thrombocytopenic patients; 13 of them with high titres of platelets-bound APA were investigated by direct and indirect MAIPA and platelet eluate analysis. Circulating APA were detected by PSIIFT in 88% of cases and 55% of controls (P = 0.0066) and platelet-bound antibodies were detected by PSIFT in 90% of cases. Indirect MAIPA detected specific APA (mainly directed against GpIIbIIIa) in 36% of cases and only 5% of the controls (P = 0.0076). Nine out of the 13 fully investigated thrombocytopenic patients (69%) had a positive direct MAIPA and/or APA detected in platelet eluates. In conclusion, the production of specific anti-platelet autoantibodies, mainly directed against GpIIb/IIIa, and their binding to platelet membrane plays an important role in the pathogenesis of SLE-associated thrombocytopenia.

BACKGROUND: CD36 is expressed on several cell lineages. About 5 to 10 percent of Asians lack platelet membrane CD36 (pCD36), but the frequency of pCD36 deficiency in other ethnic groups is not known. Persons who are pCD36‐negative are apparently healthy but can develop CD36 isoimmunization.STUDY DESIGN AND METHODS: The pCD36 phenotype was studied in 1885 subjects belonging either to a group of 1127 healthy French blood donors (almost all of whom were white Europeans) or to a group of 758 patients of known ethnic origin.RESULTS: No pCD36‐negative persons were found among the blood donors. Only 1 of the 301 white European patients was pCD36‐negative. In contrast, 16 of the 206 sub‐Saharan Africans was pCD36‐negative, a proportion higher than that among that black Caribbeans (1/148, p<0.01). The frequency of pCD36‐negative patients was similar in blacks with and without sickle cell disease. Monocyte CD36 (mCD36) expression was studied in 15 of 22 pCD36‐negative individuals: it was <10 percent in 7 subjects (type I deficiency) and between 12 and 100 percent in 8 others (type II deficiency). Thirteen pCD36‐negative individuals had risk factors for immunization, and 4 had anti‐CD36. Some had a history resembling posttransfusion purpura (n = 2), platelet transfusion refractoriness (n = 1), and recurrent miscarriage (n = 1). No correlation was found between immunization and the amount of mCD36. Anti‐CD36 from an immunized type II‐deficient woman reacted with monocytes from normal controls but not with monocytes from type I‐ or type II‐deficient individuals, and thus it is postulated that mCD36 could be structurally different in normal and type II CD36‐deficient individuals.CONCLUSION: CD36 deficiency is frequent in sub‐Saharan Africans; development of anti‐CD36 can lead to serious complications in multiply transfused patients, such as those with sicke cell disease.

Background: Irinotecan is currently used as second-line chemotherapy for advanced colorectal cancer.We report a case of severe thrombocytopenia after Irinotecan, suggesting an immune mechanism, in a 53-year-old patient.Patients and methods: The patient's sera were screened for platelet antibodies with an indirect platelet immunofluorescence test (PIIFT).The monoclonal antibody immobilization of platelet antigen assay (MAIPA) was used to characterize the antibody target.Results: We detected an IgG platelet antibody in the pa-tient's serum in the presence of Irinotecan by means of PIIFT, and not in the presence of SN-38, its active metabolite.The specificity of the binding was asserted after CD32 MoAb blockade.The platelet binding site could not be strictly identified with MAIPA and immunoblotting but GpIIb/IIIa can be excluded after experiments with Glanzmann platelets.Conclusion: This case can be considered the first documented Irinotecan-induced immune thrombocytopenia.

Polymorphic structures of the neutrophil Fcγreceptor IIIb (FcγRIIIb) result in alloantibody formation that causes alloimmune neonatal neutropenia and transfusion reactions. Alloantigens located on FcγRIIIb include the antigens NA1 and NA2. In four cases of alloimmune neonatal neutropenia, granulocyte-specific alloantibodies directed against a thus far unknown antigen were detected by granulocyte agglutination and immunofluorescence tests in the maternal sera. By the use of the monoclonal antibody–specific immobilization of granulocyte antigens (MAIGA) assay, the new antigen, termed SH, was located on the FcγRIIIb. Nucleotide sequence analysis of the FcγRIIIb coding region from a SH(+) individual showed a single-base C→A mutation at position 266, which results in an Ala78Asp amino acid substitution. A family study confirmed that this nucleotide difference is inherited, and corresponds to the SH phenotype. Serologic typing of 309 randomly selected individuals showed an antigen frequency of 5% in the white population. The same frequency was found by genotyping, for which a technique based on polymerase chain reaction (PCR) using sequence-specific primers (PCR-SSP) was developed. Typing of all SH(+) individuals for NA1 and NA2, and PCR-restriction fragment length polymorphism analysis of the NA-specific PCR products from five SH(+) individuals using the SH-specific endonuclease SfaN I showed that SH antigen is very probably the result of an additional mutational event in the NA2 form of the FcγRIIIB gene. Immunochemical studies also demonstrated that the SH determinants reside on the 65- to 80-kD NA2 isoform of the FcγRIIIb. Our findings show the existence of an additional polymorphism of the FcγRIIIb, which can result in alloantibody formation causing alloimmune neonatal neutropenia.

Thrombocytopenia is a frequent complication of primary antiphospholipid syndrome (PAPL) and has been attributed to antibodies directed against platelet glycoproteins (Gp) and also to antiphospholipid antibodies. We tested patients with PAPL with and without thrombocytopenia for specific antiplatelet autoantibodies. Platelet autoantibodies were detected by means of platelet immunoassays which included MAIPA with a panel of monoclonal antibodies directed against all the platelet Gps known to be possible targets for platelet autoantibodies. A high prevalence of serum platelet antibodies was found in patients with thrombocytopenia (73%, 11/15 patients) whereas antiplatelet antibody was detected in only one of the 10 control patients (P < 0.01). The antibodies mainly recognized GpIIbIIIa (n = 7), but also CD9 (n = 5), GpIaIIa (n = 4), GpIbIX (n = 3) and GpIV (n = 3). Platelet‐Gp antibodies eluted from the platelet surface had the same reactivity as those found in the original sera from three of the four patients tested, whereas no anticardiolipin activity was found in the platelet eluates, suggesting the absence of cross‐reactivity between anticardiolipin and antiplatlet antibodies. The MAIPA assay was also performed with F(ab′)2 fragments obtained by pepsin digestion of serum IgG from four patients. The same results were obtained with F(ab′)2 fragments and the original serum, demonstrating that platelet antibodies specifically bind in vivo to platelet Gps via their F(ab′)2 fragments. Our results suggest a link between specific platelet antibodies and the thrombocytopenia of PAPL.

Prolonged corticosteroid (CS) therapy induces osteoporosis and fractures. Osteoporosis is characterized at the histomorphometric level by reduced bone volume (BV/TV) and disruption of the three-dimensional (3D) trabecular architecture. Several stereological methods have been proposed to characterize these alterations: measurements of trabecular thickness and trabecular number, star volumes, interconnectivity index (ICI) of the bone marrow spaces, and trabecular bone pattern factor (TBP(f)). These methods were computerized with a single program running on an image analyzer to evaluate the bone changes in a series of iliac biopsies performed on 31 male patients. All of them were asthmatic and had received CS for a long period of time. BV/TV was reduced when compared with age-matched controls. In the CS-treated population, exponential relationships were obtained between bone volume and the different connectivity parameters. The various methods used to measure connectivity were well correlated. When the population was divided into two groups (BV/TV greater or less than an 11% threshold), the architectural disturbances were found to imply two mechanisms. A progressive decline in trabecular thickness was noted in both groups versus controls. Trabecular perforations were not established in the group with BV/TV> 11% with the star volume or ICI, although some alterations were detected by trabecular bone pattern factor measurement. However, perforations were revealed in the group with BV/TV < 11% by all the different methods. Perforations seemed to occur when the trabecular thickness was below 70 mu m. This strongly suggests that bone histomorphometry should take into consideration bone volume in combination with detailed 3D descriptors of the trabecular architecture. Several histological methods need to be used in combination to appreciate the 3D architecture of trabecular bone.

A study of 30 patients admitted for infectious discitis identified four cases with concomitant bacterial endocarditis. All four patients were male and had concomitant streptococcal septicemia. Two patients had known aortic valve disease. The vertebral infection was located to the thoracic or lumbar spine. Ultrasonography disclosed aortic lesions in all four patients and mitral lesions in two. Management consisted of intravenous antimicrobial therapy for four weeks followed by a three-month course of oral antimicrobial therapy. The outcome of the discitis was favorable within the usual period of time. However, the endocardial lesions continued to progress, and three patients rapidly required valve replacement. Analysis of available data in the 30 patients with discitis showed that half the patients with streptococcal discitis also had bacterial endocarditis and that the latter condition developed in all the patients with streptococcal discitis and a history of valve disease. A number of risk factors were identified. An echocardiogram should be done routinely in patients with infectious discitis and risk factors for bacterial endocarditis.

Fusidic acid is used in hospitals as second-line therapy for multidrug-resistant staphylococcal infections. We report the first fully documented case of fusidic acid induced thrombocytopenia, in a 48-year-old patient, The thrombocytopenia was abrupt and severe but resolved spontaneously 7d after drug withdrawal, The thrombocytopenia transiently relapsed 6d later, when fusidic acid was reintroduced. Haemorrhagic signs were observed, but no severe bleeding occurred, Platelet transfusions failed to increase the platelet count. We detected an IgG platelet antibody in the patient's serum, that specifically recognized platelet glycoprotein IIb/IIIa only in the presence of fusidic acid.Fusidic acid induced thrombocytopenia should be considered as a possible cause for the thrombocytopenia frequently seen in the intensive care setting.

L'analyse d'une serie de 30 patients hospitalises pour une spondylodiscite infectieuse permet de retenir chez 4 d'entre eux l'existence d'une endocardite bacterienne associee. Il s'agit de 4 hommes dont les antecedents sont marques dans 2 cas par une valvulopathie aortique ; la spondylodiscite lombaire ou dorsale est toujours associee a une septicemie a streptocoque. L'echocardiographie montre une atteinte aortique dans 2 cas, aortique et mitrale dans les 2 autres. Malgre la mise en oeuvre d'une antibiotherapie intraveineuse pendant 4 semaines, relayee par voie orale durant trois mois et l'obtention de la guerison de la spondylodiscite dans les delais habituels, la degradation de l'endocarde se poursuit et conduit a la realisation d'un remplacement valvulaire rapide chez 3 patients. L'analyse comparative des donnees disponibles pour ces 30 patients montre que l'endocardite atteint la moitie des patients porteurs d'une spondylodiscite a streptocoque et surtout semble constante chez les malades ayant a la fois une spondylodiscite a streptocoque et un antecedent valvulaire. Elle permet egalement de definir les facteurs de risque qui doivent conduire a realiser une echocardiographie lors de la prise en charge d'une spondylodiscite infectieuse.

Background: CD36 deficiency, which could lead to CD36 isoimmunization, has been reported in the Japanese population. CD36 isoantibody has been involved in platelet transfusion refractoriness.Case Report: A 50-year-old woman originally from Corsica developed severe acute thrombocytopenia after massive transfusion. She was found to be CD36 deficient, and platelet immunoassays revealed a CD36 (Nak(a)) platelet isoantibody. Although the involvement of another mechanism could not be entirely ruled out, the thrombocytopenia was attributed to posttransfusion purpura-like syndrome. The antibody was also involved in platelet transfusion refractoriness. CD36 deficiency was present in two members of the patient's family as well. Flow cytometry studies demonstrated the absence of CD36 expression on the surface of blood monocytes and cultured erythroblasts and megakaryocytes from one of the two CD36-deficient family members studied, but, in the absence of previous immunization, these CD36-deficient patients were not isoimmunized. In contrast, CD36 deficiency was not found in a population of 808 healthy blood donors in the Paris, France, area.Conclusion: CD36 isoantibody might be involved in some cases of posttransfusion purpura and platelet transfusion refractoriness. These findings also confirm the extremely low frequency of CD36 deficiency among whites.