A recent onset inflammatory polyarthritis register in Spain: factors that predict remission.

OBJECTIVE: To identify baseline variables that predict remission at 1 year in patients with recent onset inflammatory polyarthritis (IP). METHODS: We prospectively studied 167 patients aged >or=16 years with a 4-week to 12-month history of swelling of >or=2 joints. At baseline, no patient had previously received corticosteroids or disease-modifying anti-rheumatic drugs (DMARDs). To adjust for differences in baseline variables associated with the type of treatment given (a surrogate marker of disease severity), we used regression analysis. The classification probability of treatment thus obtained was entered, along with other significant baseline variables, in a second separate regression analysis to identify variables that predicted remission (no swollen joints). RESULTS: Frequency of remission was 50.9% at 1 year. In the first regression analysis, variables associated with treatment with DMARDs or DMARDs and corticosteroids versus corticosteroids alone included age, morning stiffness, swollen joint count (SJC), disease severity according to the patient, and rheumatoid factor (RF) level; the strongest association was for higher SJC. In the second regression analysis, the model that best predicted remission (correct in 70.1% of cases) included age, tender joint count (TJC), erythrocyte sedimentation rate (ESR), RF, total Sharp score, disease severity according to the physician, and the 1987 American Rheumatism Association (ARA) criteria for rheumatoid arthritis (RA); the strongest association was for failure to meet these criteria. The model's sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve were 70.6%, 70.9%, and 75.4%, respectively. CONCLUSION: Although we identified some predictors of remission, no model accurately predicted remission at 1 year in this cohort.

Anti-centromere antibodies in patients with systemic lupus erythematosus.

BACKGROUND: Anti-centromere autoantibodies (ACA) are frequently detected in systemic sclerosis (SScl), especially in the calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia (CREST) syndrome, in which a prevalence of 55% has been reported. The presence of ACA in systemic lupus erythematosus (SLE) is so rare that its detection can raise serious doubts about the validity of the diagnosis. OBJECTIVE: To determine the frequency of ACA positive subjects from a wide monocentric cohort of SLE patients and analyse the clinical and biological characteristics of this group. METHODS: Five hundred and sixty consecutive SLE patients were systematically analysed for the presence of ACA and other autoantibodies using indirect immunofluorescence, counter-immunoelectrophoresis, double immunodiffusion, enzyme-linked immunosorbent assay (ELISA), and Western-blot. RESULTS: ACA were detected in 11 SLE patients (1.9%); all of them were women. The CENP-B-specific ELISA was positive in all patients. The main clinical features of scleroderma (cutaneous sclerosis, sclerodactylia, digital ulcers, or pulmonary fibrosis) were not present in these patients, who did not differ clinically from the whole SLE group. CONCLUSIONS: ACA can be detected in patients with genuine SLE without concurrent scleroderma. Therefore, the presence of this antibody does not preclude the possibility of the diagnosis of SLE. In addition, SLE patients with ACA do not represent a different clinical subgroup.

Incremento en la incidencia de los derrames pleurales paraneumónicos / Increase in the incidence of parapneumonic pleural effusions

No disponible

Resultados del Taller de Autoinmunidad. Córdoba 2005 / No disponible

En el Congreso de la Sociedad Española de Inmunología, celebrado del 10 al 13 de mayo de 2005 en Córdoba, se analizaron 17 sueros procedentes de los 36 Laboratorios participantes en el XIX Taller de Autoinmunidad. Este año el interés se focalizó en marcadores de enfermedades autoinmunes hepáticas, fundamentalmente en las especificidades: AMA, LKM1, LC1, Actina-F, SLA, MND/Sp100, poro nuclear (gp210) y ANCA. Las técnicas empleadas fueron inmunofluorescencia indirecta (IFI), ELISA, western-blot, dot-blot e inmunoprecipitación. Se constató que son necesarias técnicas complementarias a la IFI, sobre todo en sueros de bajo título, imágenes solapadas o paraantígenos, como SLA, no discernibles por IFI. La técnica de dotblot,en general muy sensible, se mostró algunas veces insuficiente,en particular en el caso de la Actina-F y en otras dio falsos positivos por lo que debe ser interpretada también junto a otras técnicas. El western-blot, el dot-blot y el ELISA fueron más sensibles que la IFI en el estudio de los AMA. El western-blot con microsomas purificados fue la técnica menos sensible para LKM1.Se discutió la importancia de los anticuerpos anti-MND/Sp100 y poro nuclear para el diagnóstico de la cirrosis biliar primaria en ausencia de AMA. También se comentaron algunas especificidades concomitantes, fuera del contexto clínico analizado.En el ejercicio se incluyó por primera vez un CD con imágenes de IFI poco frecuentes, destinado a suplir aquellos sueros de volumen insuficiente para una amplia distribución. Si se generaliza esta iniciativa, puede llegar a constituirse un interesante archivo para consultas y docencia (AU)

During the Congress of the Spanish Society of Immunology, held in Córdoba from the 10th to 13th may 2005, the XIX Workshop on Autoimmune Diseases took place, focusing this year on the study of markers of hepatic autoimmune diseases. Seventeen sera were analysed, coming from the 36 participant laboratories. The sera included specificities like AMA, LKM1, LC1, F-actin,SLA, MND/Sp100, nuclear pore (gp210) and ANCA. The techniques used were indirect immunofluorescence (IIF), ELISA, western-blot, dot-blot and immunoprecipitation. The results allowed to state that techniques complementary to IIF are necessary to be applied, particularly in low titered sera, in overlapping patterns and in sera recognizing antigens, like SLA, not visible by IIF. Western-blot, dot-blot and ELISA M2 showed a higher sensitivity thanIIF for detecting AMA. F-actin was also underdetected by IIF. The western-blot performed with purified microsomes was less sensitive than dot-blot or ELISA for LMK1 detection. Dot-blot was a suitable technique but showed some false negative results (particularly in F-actin detection) and also false positive reactions and must be interpreted together with other techniques. Finally the discussion focused on the importance of anti-MND/Sp100 and nuclear pore complex for the diagnosis of primary biliary cirrhosis,particularly in the absence of AMA. Also some patterns,other than specific hepatic disease markers, were commented.To complete the exercise, for the first time, a CD was included containing some rare specificities of sera not available to bedistributed. If this initiative becomes established, an interesting archive for consultation and teaching may be created (AU)

Resultados del Taller de Autoinmunidad. Córdoba 2005 / Results from the XIX spanish autoimmunity workshop (Córdoba 2005)

En el Congreso de la Sociedad Española de Inmunología, celebradodel 10 al 13 de mayo de 2005 en Córdoba, se analizaron17 sueros procedentes de los 36 Laboratorios participantes en elXIX Taller de Autoinmunidad. Este año el interés se focalizó enmarcadores de enfermedades autoinmunes hepáticas, fundamentalmenteen las especificidades: AMA, LKM1, LC1, Actina-F, SLA, MND/Sp100, poro nuclear (gp210) y ANCA. Las técnicasempleadas fueron inmunofluorescencia indirecta (IFI), ELISA,western-blot, dot-blot e inmunoprecipitación.Se constató que son necesarias técnicas complementarias a laIFI, sobre todo en sueros de bajo título, imágenes solapadas o paraantígenos, como SLA, no discernibles por IFI. La técnica de dotblot,en general muy sensible, se mostró algunas veces insuficiente,en particular en el caso de la Actina-F y en otras dio falsospositivos por lo que debe ser interpretada también junto a otrastécnicas. El western-blot, el dot-blot y el ELISA fueron más sensiblesque la IFI en el estudio de los AMA. El western-blot conmicrosomas purificados fue la técnica menos sensible para LKM1.Se discutió la importancia de los anticuerpos anti-MND/Sp100y poro nuclear para el diagnóstico de la cirrosis biliar primaria enausencia de AMA. También se comentaron algunas especificidadesconcomitantes, fuera del contexto clínico analizado.En el ejercicio se incluyó por primera vez un CD con imágenesde IFI poco frecuentes, destinado a suplir aquellos suerosde volumen insuficiente para una amplia distribución. Si se generalizaesta iniciativa, puede llegar a constituirse un interesantearchivo para consultas y docencia

During the Congress of the Spanish Society of Immunology,held in Córdoba from the 10th to 13th may 2005, the XIX Workshopon Autoimmune Diseases took place, focusing this year onthe study of markers of hepatic autoimmune diseases. Seventeensera were analysed, coming from the 36 participant laboratories.The sera included specificities like AMA, LKM1, LC1, F-actin,SLA, MND/Sp100, nuclear pore (gp210) and ANCA. The techniquesused were indirect immunofluorescence (IIF), ELISA, western-blot, dot-blot and immunoprecipitation. The results allowedto state that techniques complementary to IIF are necessary to beapplied, particularly in low titered sera, in overlapping patternsand in sera recognizing antigens, like SLA, not visible by IIF. Western-blot, dot-blot and ELISA M2 showed a higher sensitivity thanIIF for detecting AMA. F-actin was also underdetected by IIF. Thewestern-blot performed with purified microsomes was less sensitivethan dot-blot or ELISA for LMK1 detection. Dot-blot was asuitable technique but showed some false negative results (particularlyin F-actin detection) and also false positive reactions andmust be interpreted together with other techniques. Finally thediscussion focused on the importance of anti-MND/Sp100 andnuclear pore complex for the diagnosis of primary biliary cirrhosis,particularly in the absence of AMA. Also some patterns,other than specific hepatic disease markers, were commented.To complete the exercise, for the first time, a CD was includedcontaining some rare specificities of sera not available to bedistributed. If this initiative becomes established, an interestingarchive for consultation and teaching may be created

Antibodies against the donor antigen glutathione S-transferase T1 after renal transplantation.

The aim of the present study was to determine whether a kidney graft expressing the glutathione S-transferase T1 enzyme (GSTT1) could cause an alloimmune response in a recipient with the null GSTT1 genotype that was similar to that observed in liver transplant. We have found anti-GSTT1 antibodies in the sera of a number of patients and confirmed that only one of the four possible genetic combinations--positive donor/null receptor--could lead to the production of these antibodies. Nevertheless, the main finding of this study is that in kidney transplantation, this mismatch was not sufficient to trigger an immune reaction. Longer follow-up of the posttransplant evolution of the patients is required in order to clarify the contribution of the factors involved in this process.

Glutathione S-transferase T1 genetic mismatch is a risk factor for de novo immune hepatitis in liver transplantation.

Glutathione S-transferase T1 (GSTT1) is a drug metabolizing enzyme abundantly expressed in liver and kidney cells; it is encoded by a single gene that is absent in 20% of the Caucasian population. Our group found that some liver transplantation patients developed de novo immune hepatitis (IH) and that all of them had anti-GSTT1 antibodies. The main objective of this study was to analyze the influence of a GSTT1 mismatch between donor and recipient in the immune response and the outcome of the graft. We confirmed that only under one of the four possible genetic combinations (null recipient/positive donor) is an alloimmune response triggered with production of anti-GSTT1 antibodies. Therefore, we conclude that this genetic mismatch can be considered a risk factor for de novo IH.

High seroprevalence of Pneumocystis infection in Spanish children.

Pneumocystis infection occurs worldwide, and most individuals test seropositive for Pneumocystis early in childhood. Little is known about the epidemiology of this infection in western Europe. The seroprevalence of Pneumocystis infection in 233 Spanish children was determined in a community study by immunoblot analysis of sera. The overall seroprevalence was 73%, with an age-related increase from 52% at 6 years to 66% at 10 years and 80% at 13 years. The data indicated a high seroprevalence of Pneumocystis infection in healthy Spanish children, thereby demonstrating that this pathogen is widespread in southern Spain.

Frecuencia de anticuerpos antinucleares en ancianos sanos / Frequency of antinuclear antibodies in the healthy elderly

Fundamento: Conocer la frecuencia de anticuerpos antinucleares (AAN) en población anciana en Andalucía. Pacientes y métodos: Se estudiaron 100 ancianos sanos (edad media, 81,6 años) y un grupo control de 199 donantes de sangre (edad media, 33,5 años). Los AAN se determinaron mediante inmunofluorescencia indirecta (IFI; sustratos triple de rata y HEp-2), los anticuerpos anti-ENA mediante contrainmunoelectroforesis y los anticuerpos anti-ADNn con IFI (Crithidia luciliae). Resultados: En ancianos, el título de AAN fue > 1/40 en el 51 por ciento y > 1/160 en el 36 por ciento (sustrato triple de rata), y > 1/40 en el 74 por ciento y > 1/160 en el 64 por ciento (sustrato HEp-2). El patrón más frecuente fue el moteado fino. Los anticuerpos anti-ADNn y antiENA fueron negativos. En controles, la frecuencia de AAN > 1/40 (HEp-2) fue del 7,5 por ciento (p < 0,001). Conclusión: La alta frecuencia de AAN en ancianos obliga a valorarlos con cautela en ausencia de indicios clinicobiológicos de enfermedad autoinmunitaria. (AU)

Clinical significance of anti-multiple nuclear dots/Sp100 autoantibodies.

BACKGROUND: Autoantibodies against discrete variable-sized dots observed in HEp2 cells by indirect immunofluorescence (IIF) test, called multiple nuclear dots (MND), have been closely associated with primary biliary cirrhosis (PBC). Some authors have argued that this antibody is also present in connective tissue diseases or liver diseases other than PBC as autoimmune chronic active hepatitis, particularly of the cholestatic type. We studied an unselected group of patients routinely tested for autoantibodies and positive for the MND pattern and tried to establish the correlation between the presence of this antibody and their diagnosis. METHODS: A commercial ELISA test, using a recombinant 26 kD truncated sequence of the Sp100 protein, corresponding to an immunodominant molecular region, was used to assess the clinical correlation of these autoantibodies in 110 patients showing an anti-MND immunofluorescence pattern. RESULTS: One-hundred-and-ten patients were MND positive by IIF. Of these, 100 were Sp100 positive by ELISA. In the Sp100 positive group, 34 had a diagnosis of PBC (30 definite and 4 suspected) while 15 patients had a non-PBC hepatopathy. Unexpectedly, 13 of the MND/Sp100 positive pattern corresponded to systemic lupus erythematosus (SLE) patients and 5 cases to collagen diseases. Another divergence with previous reports was that 34 of the positive patients showed very heterogeneous clinical pictures, different from hepatopathies or collagen diseases. CONCLUSIONS: Anti-Sp100 antibodies can be found in many clinical conditions. Testing for MND/Sp100 positivity is useful for the diagnosis of PBC, but only when the right clinical context is present. Other diseases cannot be excluded in first line SLE.

Complement component C7 deficiency in a Spanish family.

Different genetic mutations have been described in complement component C7 deficiency, a molecular defect which is clinically associated with an increased susceptibility to neisserial recurrent infections, although some cases remain asymptomatic. In this work we report the genetic bases of C7 deficiency in one Spanish family. Exon-specific PCR and sequencing revealed a novel point mutation at nucleotide 615 (exon 6) leading to a stop codon (UGG to UGA) in the patient, his mother, and sister. This transversion causes the premature truncation of the C7 protein (W183X). Additionally, we detected a missense mutation at position 1135 (exon 9) located in the first nucleotide of the codon GGG (CGG), resulting in an amino acid change (G357R) in the patient, his father, as well as in his sister. This latter mutation had been previously described in individuals from Moroccan Sephardic Jewish ancestry. Since both heterozygous mutations were found in the patient as well as in his asymptomatic sister, we analyse other meningococcal defence mechanisms such as polymorphisms of the opsonin receptors on polymorphonuclear cells. Results showed that the patient and his sister bore identical combinations of FcgammaRIIA-H/R131 and FcgammaRIIIB-NA1/2 allotypes. Our results provide further evidence that the molecular pathogenesis of C7 deficiency as well as susceptibility to meningococcal disease are heterogeneous, since different families carry different molecular defects, although many of the C7 defects appear to be homogeneous in individuals from certain geographical areas. The missense mutation G357R would make an interesting topic of analysis with regard to meningococcal disease susceptibility in the Spanish population.

[Iliopsoas abscess and systemic lupus erythematosus]. / Absceso del músculo iliopsoas y lupus eritematoso sistémico.

Iliopsoas muscle abscess (IPA) is an uncommon condition, and it is usually associated with immunosuppression. Three out of a cohort of 552 patients diagnosed of systemic lupus erythematosus (SLE) developing an IPA, are reported herein. Patients showed fever and other symptoms related to SLE. They improved only partially under SLE therapy, and showed pain suggestive of IPA. It was confirmed by CT in all cases. S. aureus was isolated in one patient (primary IPA), and M. tuberculosis in the others. Specific antimicrobial therapy and surgical drainage were required. In summary, SLE might be considered as a risk condition for the development of IPA, due to the immunosuppression inherent in the disease and its treatment.

Absceso del músculo iliopsoas y lupus eritematoso sistémico / Iliopsoas abscess and systemic lupus erythematosus

El absceso del músculo iliopsoas (AIP) es una patología infrecuente, que se asocia a situaciones de inmunodeficiencia. Se presentan 3 casos de lupus eritematoso sistémico (LES), de una serie de 552 pacientes, que desarrollaron un AIP. El cuadro clínico se caracterizó por fiebre y otras manifestaciones relacionadas con su enfermedad de base, que cursaron de forma tórpida hasta que apareció dolor sugestivo de la existencia de un AIP. El agente etiológico fue S. aureus en un paciente (AIP primario), y M. tuberculosis en los otros 2 (AIP secundario). Para su tratamiento se requirió, además de antibioterapia específica, drenaje quirúrgico de la colección (fracaso previo del drenaje percutáneo en 2 casos). En la opinión de los autores, el LES, por la inmunodepresión subyacente relacionada tanto con la enfermedad en sí como con la medicación utilizada en el tratamiento, debe incluirse entre las circunstancias de riesgo para el desarrollo de AIP. (AU)

Antibodies against glutathione S-transferase T1 (GSTT1) in patients with de novo immune hepatitis following liver transplantation.

Four patients of 283 liver-transplant recipients (1.4%) developed de novo immune-mediated hepatitis approximately 2 years after transplantation. Antibodies showing an unusual liver/kidney cytoplasmic staining pattern were detected in the sera of all four patients and one of them was used to screen a human liver cDNA expression library with the aim of identifying the antigenic target of these newly developed antibodies. After cloning and sequencing the gene, it was identified as the gene encoding the glutathion-S-transferase T1 (GSTT1), a 29-kD molecular weight protein, expressed abundantly in liver and kidney. Sera from the other three patients also contained anti-GSTT1 antibodies, two of them demonstrated by immunoblot analysis against the recombinant antigen and the other, which was negative by immunoblot, gave a positive reaction when used directly to screen the same library, suggesting it to be directed to a conformational epitope. The GSTT1 enzyme is the product of a single polymorphic gene that is absent from 20% of the Caucasian population. When we analysed the GSTT1 genotype of the four patients described above, we found that this gene is absent from all of them. Three donor paraffin embedded DNA samples were available and were shown to be positive for GSSTT1 genotype. In accordance with these results, we suggest that this form of post-transplant de novo immune hepatitis, that has been reported as autoimmune hepatitis by others, could be the result of an antigraft reaction in individuals lacking the GSTT1 phenotype, in which the immune system recognizes the GSTT1 protein as a non-self antigen, being the graft dysfunction not the result of an autoimmune reaction, but the consequence of an alo-reactive immune response.

Autoantibodies to DEK oncoprotein in systemic lupus erythematosus (SLE).

Autoantibodies against the transcriptional DEK protein have been considered characteristic of the pauciarticular onset subtype of juvenile rheumatoid arthritis (JRA) associated with iridocyclitis in young girls. In this study we investigated the presence of anti-DEK autoantibodies in the sera of 288 patients with SLE using a recombinant DEK protein as autoantigenic target. Thirty sera (10.4%) were positive against DEK protein by immunoblotting. Patients with anti-DEK autoantibodies show a lower frequency of cutaneous manifestation, exhibit more frequently certain markers of a chronic inflammatory status like anaemia and positivity for C-reactive protein, as well as a higher frequency of anti-double-stranded DNA autoantibodies. In contrast to JRA patients positive for anti-DEK autoantibodies, no association with erosive arthritis nor iridocyclitis were found in SLE. In conclusion, our results show that 10.4% of SLE patients from our area show antibodies against DEK protein, although this feature did not clearly establish a clinical subset of the disease.

Identification of cation-independent mannose 6-phosphate receptor/insulin-like growth factor type-2 receptor as a novel target of autoantibodies.

Two human monoclonal autoantibodies, B-33 and B-24, were generated from the B cells of a patient with scleroderma. Both monoclonal antibodies (mAbs) were composed of mu and lambda chains, and recognized cytoplasmic vesicular structures by indirect immunofluorescence on Hep-2 cell line slides, although mAb B-24 showed an additional diffuse cytoplasmic staining pattern. By Western blot, mAb B-24 exhibited a polyreactive-like binding pattern, whereas mAb B-33 failed to recognize any electroblotted Hep-2 antigen. The polyreactive versus monospecific behaviour of mAbs B-24 and B-33 was further confirmed by enzyme-linked immunosorbent assay (ELISA) with a variety of foreign and autoantigens. The N-terminal sequence of a protein band isolated by affinity chromatography with mAb B-33 was identical to that of cation-independent mannose 6-phosphate receptor (CI-MPR), also known as the insulin-like growth factor type-2 receptor (IGF-2R). Immunofluorescence experiments on Hep-2 cell line slides demonstrated a striking co-localization between the staining pattern exhibited by these mAbs and the pattern obtained using a goat anti-CI-MPR serum, indicating the recognition by B-24 and B-33 of a structure located predominantly in late endosomes. Sequence analysis of the V-region gene segments of B-33 and B-24 showed both to be identical, except for the existence of a point mutation in B-33 located in the H-complementarity-determining region 3 (H-CDR3) (position 100D), which produces a non-conservative replacement of Gly by Ser. This single replacement appears to be responsible for the dramatic change in reactivity of human mAb B-33. The data shown here provide new evidence of the critical role played by the H-CDR3 region in distinguishing a polyspecific from a monospecific antibody. A population study demonstrated the existence of immunoglobulin G (IgG) reactivity against CI-MPR/IGF-2R in serum specimens from five individuals with different pathological conditions, thus indicating that this molecule is a potential target for the human autoimmune response.

Autoimmune deafness is not related to hyperreactivity to type II collagen.

The pathogenic role of anti-type II collagen was analysed in a variety of hearing losses, in age-matched controls and in different autoimmune diseases. The immune reactivity of peripheral blood lymphocytes to type II collagen was studied by the degree of proliferation measured as the incorporation of bromodeoxyuridine in cultured lymphocytes. The anti-type II collagen antibodies showed a very low incidence in the hearing loss group. Lymphocytes of otosclerosis, Meniere's disease and other sensorineural deafness patients proliferated in response to concanavalin A and to type II collagen to a lower extent than peripheral blood lymphocytes from healthy controls. Nonetheless, these differences were not statistically significant. The immune hyperreactivity to type II collagen cannot explain the autoimmune mechanism of hearing losses. Humoral and cellular hyperreactivities to inner ear proteins different from type II collagen, could explain the autoimmune mechanism of deafness.

[Anti-Sp100 and anti-Gp210 in the diagnosis of primary biliary cirrhosis in patients with autoimmune cholangitis]. / Anti-Sp100 y anti-Gp210 en el diagnóstico de cirrosis biliar primaria en pacientes con colangitis autoinmune.

We describe 2 women with features of autoimmune cholangitis. Serum biochemical studies showed cholestasis and increased immunoglobulin M with negative antimitochondrial antibodies. Markers of hepatitis B and C viruses were absent. Both had positive antinuclear antibodies. One had a speckled pattern (multiple nuclear dots) and the other a perinuclear pattern (pore nuclear). In the first case anti-Sp100 was positive by EIA and in the second anti-Gp210 was detected by immunoblot. Diagnosis of primary biliary cirrhosis was made and the patients were treated with UDCA. Current knowledge indicates that determination of anti-Sp100 and anti-Gp210 substantially improves diagnosis of primary biliary cirrhosis as these ANA are highly specific for this disease. These autoantibodies may lead to the classification of different groups of patient included in autoimmune cholangitis. All patients with autoimmune cholangitis should be tested for anti-Sp100 and anti-Gp210.