Prevalencia de anticuerpos anticitoplasma de neutrófilos en pacientes con artritis psoriática / Prevalence of antibodies anticytoplasm of neutrophils in patients with Psoriatic Arthritis

Los anticuerpos anticitoplasma de neutrófilos (ANCA) han cobrado relevancia en distintas patologías. Recientemente se ha reportado un elevado porcentaje (79%) de ANCAp en pacientes con Artropatía Psoriática (APs). Los objetivos de este estudio fueron evaluar la prevalencia ANCAp en pacientes con APs y compararlo con pacientes con artritis reumatoidea (AR), espondilitis anquilosante (EA), psoriasis cutánea (Ps) y controles sanos (CS). Material y métodos: Se incluyeron pacientes consecutivos con APs según criterios CASPAR, AR (criterios ACR 87), EA (criterios de NY modificados); los CS fueron personas de la población general sin antecedentes o evidencias de enfermedades inmunológicas. Se excluyeron pacientes con antecedentes oncológicos, infecciosos, sarcoidosis u otras enfermedades del tejido conectivo y/o vasculitis. Se consignaron datos demográficos, clínicos, radiológicos, antecedentes familiares y terapéutica actual. Se realizaron cuestionarios de actividad de enfermedad y capacidad funcional: BASDAI, BASFI, PASI y HAQ. Se extrajeron muestras de sangre para determinación de ANCA por IFI en etanol que posteriormente fueron confirmadas por IFI en formol. Se realizó además laboratorio general de rutina. Análisis estadístico: Las variables continuas fueron comparadas por ANOVA o test Student y las variables categóricas por Chi-cuadrado o test de Fisher. Resultados: Se incluyeron 148 pacientes (APs = 43, EA = 22, AR = 41, Controles = 38, Psoriasis cutánea = 4). La mediana de edad fue de 52 años (RIQ: 39,5-59), 66% eran mujeres. En el análisis intergrupo, las EA eran más jóvenes y más frecuentemente (87%) de sexo masculino. El resto de los grupos eran comparables para todas las variables demográficas. 57 pacientes mostraron fluorescencia positiva en etanol: AR: 25 (61%), APs: 14 (32,6%), EA: 11 (50%), CS: 6 (15,8%) y Ps: 1 (25%).

Antibodies ANCA are important diagnostic tools in different diseases. Recently it has been shown that these antibodies can be observed in 79% of patients with Psoriatic Arthritis (PsA). The purpose of our study was to determine the prevalence of ANCA in patients with PsA and compared to patients with Rheumatoid Arthritis (RA), Ankylosing Spondylitis (AS), Psoriasis (Ps) and healthy controls (HC). Material and methods: Consecutive patients with PsA (CASPAR criteria), RA (ACR ’87) and AS (New York criteria) were included. HC were people of the general population without evidence of immunological diseases. Patients with a previous history of oncologic, infectious diseases and sarcoidosis were excluded. Demographic, clinical, radiological and therapeutic data were collected. Disease activity and functional capacity were evaluated using validated and specific questionnaires (BASDAI, BASFI, PASI, and HAQ). ANCAs were determined by indirect immunofluorescence (IIF) on ethanol. Then, the positive ones were confirmed by IIF on formol. Student test, ANOVA, Chi square and Fisher exact test were used for Statistical analysis. Results: 148 patients were included (PsA = 43, AS = 22, RA = 41, Ps = 4 y HC = 38). Median age was 52 years (IQR: 39.5 – 59), 66% were women. AS patients were younger and more frequently men. Other variables were comparable between groups. 57 patients exhibited positive ethanol fluorescence: RA: 25 (61%), PsA: 14 (32.6%), AS: 11 (50%), HC: 6 (15.8%) and Ps: 1 (25%). However only 5 patients showed formol fluorescence: AS: 4/22 (ANCAp = 2, ANCAc = 2) y RA: 1/41 (ANCAp). The frequency of positive ANCA was significantly greater in AS vs. RA (p = 0.046).

Prevalencia de anticuerpos anticitoplasma de neutrófilos en pacientes con artritis psoriática / Prevalence of antibodies anticytoplasm of neutrophils in patients with Psoriatic Arthritis

Los anticuerpos anticitoplasma de neutrófilos (ANCA) han cobrado relevancia en distintas patologías. Recientemente se ha reportado un elevado porcentaje (79%) de ANCAp en pacientes con Artropatía Psoriática (APs). Los objetivos de este estudio fueron evaluar la prevalencia ANCAp en pacientes con APs y compararlo con pacientes con artritis reumatoidea (AR), espondilitis anquilosante (EA), psoriasis cutánea (Ps) y controles sanos (CS). Material y métodos: Se incluyeron pacientes consecutivos con APs según criterios CASPAR, AR (criterios ACR 87), EA (criterios de NY modificados); los CS fueron personas de la población general sin antecedentes o evidencias de enfermedades inmunológicas. Se excluyeron pacientes con antecedentes oncológicos, infecciosos, sarcoidosis u otras enfermedades del tejido conectivo y/o vasculitis. Se consignaron datos demográficos, clínicos, radiológicos, antecedentes familiares y terapéutica actual. Se realizaron cuestionarios de actividad de enfermedad y capacidad funcional: BASDAI, BASFI, PASI y HAQ. Se extrajeron muestras de sangre para determinación de ANCA por IFI en etanol que posteriormente fueron confirmadas por IFI en formol. Se realizó además laboratorio general de rutina. Análisis estadístico: Las variables continuas fueron comparadas por ANOVA o test Student y las variables categóricas por Chi-cuadrado o test de Fisher. Resultados: Se incluyeron 148 pacientes (APs = 43, EA = 22, AR = 41, Controles = 38, Psoriasis cutánea = 4). La mediana de edad fue de 52 años (RIQ: 39,5-59), 66% eran mujeres. En el análisis intergrupo, las EA eran más jóvenes y más frecuentemente (87%) de sexo masculino. El resto de los grupos eran comparables para todas las variables demográficas. 57 pacientes mostraron fluorescencia positiva en etanol: AR: 25 (61%), APs: 14 (32,6%), EA: 11 (50%), CS: 6 (15,8%) y Ps: 1 (25%).(AU)

Antibodies ANCA are important diagnostic tools in different diseases. Recently it has been shown that these antibodies can be observed in 79% of patients with Psoriatic Arthritis (PsA). The purpose of our study was to determine the prevalence of ANCA in patients with PsA and compared to patients with Rheumatoid Arthritis (RA), Ankylosing Spondylitis (AS), Psoriasis (Ps) and healthy controls (HC). Material and methods: Consecutive patients with PsA (CASPAR criteria), RA (ACR 87) and AS (New York criteria) were included. HC were people of the general population without evidence of immunological diseases. Patients with a previous history of oncologic, infectious diseases and sarcoidosis were excluded. Demographic, clinical, radiological and therapeutic data were collected. Disease activity and functional capacity were evaluated using validated and specific questionnaires (BASDAI, BASFI, PASI, and HAQ). ANCAs were determined by indirect immunofluorescence (IIF) on ethanol. Then, the positive ones were confirmed by IIF on formol. Student test, ANOVA, Chi square and Fisher exact test were used for Statistical analysis. Results: 148 patients were included (PsA = 43, AS = 22, RA = 41, Ps = 4 y HC = 38). Median age was 52 years (IQR: 39.5 ¹ 59), 66% were women. AS patients were younger and more frequently men. Other variables were comparable between groups. 57 patients exhibited positive ethanol fluorescence: RA: 25 (61%), PsA: 14 (32.6%), AS: 11 (50%), HC: 6 (15.8%) and Ps: 1 (25%). However only 5 patients showed formol fluorescence: AS: 4/22 (ANCAp = 2, ANCAc = 2) y RA: 1/41 (ANCAp). The frequency of positive ANCA was significantly greater in AS vs. RA (p = 0.046).(AU)

Amerindian ancestry in Argentina is associated with increased risk for systemic lupus erythematosus.

Previous studies have demonstrated that in admixed populations, West African ancestry is associated with an increased prevalence of systemic lupus erythematosus (SLE). In the current study, the effect of Amerindian ancestry in SLE was examined in an admixed population in Argentina. The Argentine population is predominantly European with approximately 20% Amerindian admixture, and a very small (<2%) contribution from West Africa. The results indicate that Amerindian admixture in this population is associated with a substantial increase in SLE susceptibility risk (Odds Ratio=7.94, P=0.00006). This difference was not due to known demographic factors, including site of collection, age and gender. In addition, there were trends towards significance for Amerindian ancestry influencing renal disease, age of onset and anti-SSA antibodies. These studies suggest that populations with Amerindian admixture, like those with West African admixture, should be considered in future studies to identify additional allelic variants that predispose to SLE.

No evidence of association between genetic variants of the PDCD1 ligands and SLE.

PDCD1, an immunoreceptor involved in peripheral tolerance has previously been shown to be genetically associated with systemic lupus erythematosus (SLE). PDCD1 has two ligands whose genes are located in close proximity on chromosome 9p24. Our attention was drawn to these ligands after finding suggestive linkage to a marker (gata62f03, Z=2.27) located close to their genes in a genome scan of Icelandic families multiplex for SLE. Here, we analyse Swedish trios (N=149) for 23 single nucleotide polymorphisms (SNPs) within the genes of the PDCD1 ligands. Initially, indication of association to eight SNPs was observed, and these SNPs were therefore also analysed in Mexican trios (N=90), as well as independent sets of patients and controls from Sweden (152 patients, 448 controls) and Argentina (288 patients, 288 controls). We do not find support for genetic association to SLE. This is the first genetic study of SLE and the PDCD1 ligands and the lack of association in several cohorts implies that these genes are not major risk factors for SLE.

Regulation of differentiation of peritoneal B-1a (CD5+) B cells. Activated peritoneal macrophages release prostaglandin E2, which inhibits IgM secretion by peritoneal B-1a cells.

The B-1a (CD5+) subset of B cells comprises the majority of B cells in the peritoneal cavity and is implicated in the pathogenesis of certain autoimmune diseases and lymphoproliferative disorders. When we stimulated purified B-1a cells with LPS, they produced more than four times as much IgM as similarly stimulated whole peritoneal cells (containing the same number of B-1a cells). Reconstitution experiments using FACS-purified peritoneal cell populations revealed that resident peritoneal macrophages (Mac1+, B220-) profoundly inhibited the LPS response of peritoneal B-1a cells. Culture of B-1a cells with peritoneal macrophages at a ratio of 3:1 (reflecting the in vivo ratio) resulted in a fivefold or greater reduction in the IgM response to LPS. LPS activation of macrophages resulted in production of a soluble factor that inhibited LPS-induced B cell differentiation by 86% when used at a concentration of 5%. When [3H]arachidonic acid-pulsed macrophages were stimulated with LPS, the major arachidonic acid metabolite secreted was PGE2 (a potent inhibitor of B cell differentiation). The inhibitory capacity of the macrophage-derived supernatant was reversed by the addition of anti-PGE2. These findings indicate that macrophage-derived PGE2 functions as an important regulator of polyclonal response of B-1a cells to LPS.

Regulation of apoptosis in vitro in mature murine spleen T cells.

Previously it has been shown that thymocytes undergo apoptosis, a form of programmed cell death, in response to glucocorticoids. This classic form of apoptosis is prevented by inhibition of protein synthesis. The current paper demonstrates that mature T cells also undergo apoptosis, but that the regulation of apoptosis in spleen T cells differs from that of thymocytes. Mature mouse spleen T cells were shown to die by apoptosis, not necrosis, when cultured without an added stimulus. Assays for apoptosis included internucleosomal DNA cleavage by gel electrophoresis, percent fragmentation of DNA by the diphenylamine method, and percent of cells with hypodiploid DNA by flow cytometry. The percent of apoptotic cells was 2% in fresh spleen T cells, and increased at least until 16 h, when 21% were apoptotic. Dexamethasone caused apoptosis in both thymus and spleen T cells, but only thymocytes showed a requirement for protein synthesis in dexamethasone-induced death. Cycloheximide increased apoptosis in spleen T cells, indicating that apoptosis was controlled by newly synthesized protective proteins. Spontaneous apoptosis was decreased in spleen T cells by protein kinase C activation, and was increased by H7 and staurosporine, which inhibits protein kinases, in contrast with the behavior of thymocytes. The protein kinase A/G inhibitor HA1004 also decreased spleen T cell apoptosis. The contrasting effects of cycloheximide on thymocytes and spleen T cells occurred over the same concentration range, and the same was true for PMA. The dexamethasone dose-response curves were similar, except that a greater proportion of spleen T cells were dexamethasone-resistant. These data support the hypothesis that the apoptosis program in T cells undergoes a transition during their maturation, such that apoptosis in mature T cells is regulated more like that of mature B cells than that of thymocytes.

Apoptosis in splenic B lymphocytes. Regulation by protein kinase C and IL-4.

Small dense splenic B lymphocytes from adult specific pathogen-free mice were shown to undergo apoptosis in vitro as indicated by internucleosomal DNA fragmentation, hypodiploid DNA content of isolated nuclei, and morphologic features by electron microscopy. Unstimulated cultures showed spontaneous apoptosis increasing gradually and monotonically from < 2 to 32% of B cells by 16 h. The rate of accumulation of apoptotic cells was reduced by the addition of IL-4 or PMA, but not by the inactive phorbol ester, 4 alpha PDD. In contrast, inhibitors of protein kinase C (H7 and staurosporine) increased the percentage of cells undergoing apoptosis to > 70% by 12 h; HA 1004, genistein, and herbimycin A all had no effect on apoptosis. Thus, protein kinase C activity regulates apoptosis, but there is no evidence that protein kinases A and G and tyrosine kinases are involved. Cycloheximide increased apoptosis, indicating that apoptosis may be restrained in B cells by the presence of one or more labile protective proteins. The percentage of apoptotic cells measured by flow cytometry and the percentage of fragmented DNA measured by the diphenylamine method were nearly equal, regardless of the method of apoptotic regulation. Together with the absence of nuclei with flow cytometric properties intermediate between normal and apoptotic, these results suggest that in individual B cells apoptosis progresses rapidly to completion. These data suggest a fundamental change in our concept of the life-style of the "resting" B cell: instead of a dormant cell remaining unchanged until it receives activation signals, the mature spleen B cell appears programmed to die by apoptosis unless rescued by specific agents, such protein kinase C activators or IL-4.

Mycobacterium gastri arthritis: septic arthritis due to Mycobacterium gastri in a patient with a renal transplant.

We describe an 18-year-old man with a renal transplant who developed septic metacarpophalangeal arthritis due to Mycobacterium gastri. He had several episodes of crystal induced synovitis, and treatment with intraarticular steroids was complicated 3 months later by iatrogenic septic arthritis. Appropriate treatment based on in vitro drug susceptibility was successful. This seems to be the first case of articular infection and the third report of human infection caused by this atypical mycobacteria.