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PURPOSE OF REVIEW: Amyloid A (AA) amyloidosis is an organ- or life-threatening complication of chronic inflammatory disorders. Here, we review the epidemiology, causes, pathogenesis, clinical features, and diagnostic and therapeutic strategies of AA amyloidosis. RECENT FINDINGS: The incidence of AA amyloidosis has declined due to better treatment of the underlying diseases. Histopathological examination is the gold standard of diagnosis, but magnetic resonance imaging can be used to detect cardiac involvement. There is yet no treatment option for the clearance of amyloid fibril deposits; therefore, the management strategy primarily aims to reduce serum amyloid A protein. Anti-inflammatory biologic agents have drastically expanded our therapeutic armamentarium. Kidney transplantation is preferred in patients with kidney failure, and the recurrence of amyloidosis in the allograft has become rare as transplant recipients have started to benefit from the new agents. The management of AA amyloidosis has been considerably changed over the recent years due to the novel therapeutic options aiming to control inflammatory activity. New agents capable of clearing amyloid deposits from the tissues are still needed.
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Amiloidosis , Humanos , Amiloidosis/diagnóstico , Amiloidosis/terapia , Proteína Amiloide A Sérica , Trasplante de RiñónRESUMEN
Background/aim: In this prospective study, we aimed to investigate the association of serum (s) and urine (u) IP-10, galectin-9, and SIGLEC-1 with disease activity in patients with systemic lupus erythematosus (SLE). Materials and methods: Sixty-three patients with active SLE (31 renal, 32 extrarenal) were included. Thirty patients with inactive SLE (15 renal, 15 extrarenal), 17 with renal active AAV, and 32 healthy volunteers were selected as control groups. Serum and urine IP-10, galectin-9, and SIGLEC-1 were tested using ELISA. Results: Levels of sIP-10 (p = 0.046), uIP-10 (p < 0.001), sGalectin-9 (p = 0.03), and uSIGLEC-1 (p = 0.006) were significantly higher in active SLE group compared to the inactive SLE; however, no differences were detected in the comparison of uGalectin-9 (p = 0.18) and sSIGLEC-1 (p = 0.69) between two groups. None of the biomarkers discriminated patients with active renal SLE from active extrarenal SLE. ROC analyses revealed an AUC of 0.63 (0.52-0.73) for sIP-10, 0.78 (0.68-0.86) for uIP-10, 0.64 (0.53-0.74) for sGalectin-9, and 0.68 (0.57-0.77) for uSIGLEC-1 in discriminating disease activity in SLE, which did not outperform C3 (0.75, 0.64-0.84) and C4 (0.72, 0.61-0.82). sIP-10 (p = 0.001), uIP-10 (p = 0.042), and uGalectin-9 (p = 0.009) were significantly increased in patients with active renal SLE compared to active renal AAV. sGalectin-9 (p < 0.001) and sIP-10 levels (p = 0.06) were decreased after 8 (5-22.5) months of treatment. Conclusion: sIP-10, uIP-10, sGalectin-9, and uSIGLEC-1 reflect global disease activity in SLE but do not outperform C3 and C4. sIP-10 and uIP-10 may be specific for active SLE compared to active AAV. sIP-10 and sGalectin-9 might be valuable in monitoring response after treatment.
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Biomarcadores , Quimiocina CXCL10 , Galectinas , Lupus Eritematoso Sistémico , Lectina 1 Similar a Ig de Unión al Ácido Siálico , Humanos , Lupus Eritematoso Sistémico/orina , Lupus Eritematoso Sistémico/sangre , Femenino , Masculino , Biomarcadores/sangre , Biomarcadores/orina , Adulto , Galectinas/sangre , Galectinas/orina , Quimiocina CXCL10/sangre , Quimiocina CXCL10/orina , Lectina 1 Similar a Ig de Unión al Ácido Siálico/sangre , Lectina 1 Similar a Ig de Unión al Ácido Siálico/orina , Persona de Mediana Edad , Estudios Prospectivos , Adulto Joven , Estudios de Casos y ControlesRESUMEN
Background/aim: In this cross-sectional study, it was aimed to test the predictive value of noncriteria antiphospholipid antibodies (aPL) in addition to the global antiphospholipid syndrome score (GAPSS) in predicting vascular thrombosis (VT) in a cohort of patients with APS and aPL (+) systemic lupus erythematosus (SLE). Material and methods: This study included 50 patients with primary APS, 68 with SLE/APS, and 52 with aPL (+) SLE who were classified according to VT as VT ± pregnancy morbidity (PM), PM only or aPL (+) SLE. Antiphospholipid serology consisting of lupus anticoagulant (LA), anticardiolipin (aCL) immunoglobulin G (IgG)/IgM/IgA, antibeta2 glycoprotein I (aß2GPI) IgG/IgM/IgA, antiphosphatidylserine/prothrombin (aPS/PT) IgG/IgM and antidomain-I (aDI) IgG was determined for each patient. The GAPSS and adjusted GAPSS (aGAPSS) were calculated for each patient, as previously defined. Logistic regression analysis was carried out with thrombosis as the dependent variable and high GAPSS, aCL IgA, aß2GPI IgA, and aDI IgG as independent variables. Results: The mean GAPSS and aGAPSS of the study population were 11.6 ± 4.4 and 9.6 ± 3.8. Both the VT ± PM APS (n = 105) and PM only APS (n = 13) groups had significantly higher GAPSS and aGAPSS values compared to the aPL (+) SLE (n = 52) group. The patients with recurrent thrombosis had higher aGAPSS but not GAPSS than those with a single thrombotic event. The computed area under the receiver operating characteristic curve demonstrated that a GAPSS ≥13 and aGAPSS ≥10 had the best predictive values for thrombosis. Logistic regression analysis including a GAPSS ≥13, aCL IgA, aß2GPI IgA, and aDI IgG showed that none of the factors other than a GAPSS ≥13 could predict thrombosis. Conclusion: Both the GAPSS and aGAPSS successfully predict the thrombotic risk in aPL (+) patients and aCL IgA, aß2GPI IgA, and aDI IgG do not contribute to high a GAPSS or aGAPSS.
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Anticuerpos Antifosfolípidos , Síndrome Antifosfolípido , Trombosis , Humanos , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/inmunología , Femenino , Adulto , Masculino , Trombosis/etiología , Trombosis/sangre , Trombosis/inmunología , Estudios Transversales , Anticuerpos Antifosfolípidos/sangre , Medición de Riesgo , Persona de Mediana Edad , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/sangre , Embarazo , Anticuerpos Anticardiolipina/sangreRESUMEN
OBJECTIVE: To identify the different clinical phenotypes of antiphospholipid syndrome (APS) by using cluster analysis and describe cumulative damage of disease clusters. METHODS: This retrospective study includes patients with APS (±systemic lupus erythematosus (SLE)). Two-step cluster analysis was applied by considering clinical data. Damage was calculated for all patients by applying damage index for APS (DIAPS). RESULTS: A total of 237 patients (198 females; median age of 43 years; median follow-up of 9.5 years) were classified into four clusters. Cluster 1 (n = 74) consisted of older patients with arterial-predominant thrombosis, livedo reticularis, and increased cardiovascular risk; cluster 2 (n = 70) of SLE+APS patients with thrombocytopenia and heart valve disease; cluster 3 (n = 59) of patients with venous-predominant thrombosis, less extra-criteria manifestations; and cluster 4 (n = 34) of patients with only pregnancy morbidity with lower frequency of extra-criteria features and cardiovascular risk. Patients with SLE+APS (n = 123) had the highest mean DIAPS. Regarding clusters, 1 and 2 had high cumulative damage. While cumulative survival rates of clusters did not differ, cluster 2 and 3 had lower survival rates at further years. There was no correlation between DIAPS and mortality. CONCLUSION: SLE+APS patients with extra-criteria manifestations and older APS patients with arterial thrombosis and increased cardiovascular risk have higher cumulative damage. Effective treatment of SLE disease activity and control of cardiovascular risk may help to reduce cumulative damage in these patients.
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Síndrome Antifosfolípido , Lupus Eritematoso Sistémico , Trombosis , Trombosis de la Vena , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/epidemiología , Femenino , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/epidemiología , Embarazo , Estudios Retrospectivos , Trombosis/epidemiología , Trombosis/etiologíaRESUMEN
The adjusted global antiphospholipid syndrome score (aGAPSS) is a recently developed thrombotic risk assessment score that considers the antiphospholipid antibody (aPL) profile and conventional cardiovascular risk factors. In this retrospective study, we aimed to evaluate the validity of the aGAPSS in predicting clinical manifestations (criteria and extra-criteria) of antiphospholipid syndrome (APS) in a single centre cohort of patients. Ninety-eight patients with APS ± systemic lupus erythematosus (SLE) were classified according to clinical manifestations as vascular thrombosis (VT), pregnancy morbidity (PM) or both (VT + PM). The aGAPSS was calculated for each patient as previously defined. Mean aGAPSS of the cohort was calculated as 10.2 ± 3.8. Significantly higher aGAPSS values were seen in VT (n = 58) and VT + PM (n = 29) groups when compared to PM (n = 11) group (10.6 ± 3.7 vs 7.4 ± 2.9, P = 0.005; 10.7 ± 4 vs 7.4 ± 2.9, P = 0.008, respectively), mainly due to lower frequencies of cardiovascular risk factors in PM. Higher aGAPPS values were also associated with recurrent thrombosis (11.6 ± 3.7 vs 9.9 ± 3.6, P = 0.04). Regarding extra-criteria manifestations, patients with livedo reticularis (n = 11) and APS nephropathy (n = 9) had significantly higher aGAPSS values (12.9 ± 3.4 vs 9.9 ± 3.7, P = 0.02; 12.4 ± 2.9 vs 10 ± 3.8, P = 0.04, respectively). The computed AUC demonstrated that aGAPSS values ≥10 had the best diagnostic accuracy for thrombosis. Our results suggest that patients with higher aGAPSS values are at higher risk for developing vascular thrombosis (either first event or recurrence) and extra-criteria manifestations, especially livedo reticularis and APS nephropathy.
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Síndrome Antifosfolípido/complicaciones , Medición de Riesgo , Trombosis/etiología , Adulto , Anticuerpos Antifosfolípidos/análisis , Síndrome Antifosfolípido/diagnóstico , Femenino , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Masculino , Persona de Mediana Edad , Embarazo , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/etiología , Estudios Retrospectivos , Trombosis/diagnóstico , Turquía/epidemiologíaRESUMEN
Objectives: Prophylactic acid suppression with proton pump inhibitors or H2 receptor antagonists is often administered after kidney transplantation. The Association of proton pump inhibitors or H2 receptor antagonists with acute rejection, hypomagnesemia, and graft loss in kidney transplant recipients is not well established. Material and Methods: We performed a retrospective cohort study of 302 kidney transplant recipients at one center (57% male; mean age 35.5±11.2 years) with more than 6 months post-transplant follow-up. Recipients were grouped according to gastric acid prophylaxis: only proton pump inhibitors (n=179), only H2 receptor antagonists (n=42), proton pump inhibitors and H2 receptor antagonists (n=55), and nonusers (n=26). The primary outcome was biopsy-proven acute rejection. Graft loss and hypomagnesemia were defined as secondary outcomes. Results: Nonusers were younger and mostly under steroid-free immunosuppression compared to other study groups (p=0.030 and p=0.009, respectively). The primary outcome was similar across study groups (p=0.266). Kaplan-Meier analyses also demonstrated similar 10-year graft survival rates: 95.5% for proton pump inhibitors, 97.6% for H2 receptor antagonists, 100% for proton pump inhibitors/H2 receptor antagonists, and 96.2% for nonusers (p=0.275). Conclusions: The use of proton pump inhibitors is not associated with acute rejection or graft loss but may cause mild hypomagnesemia in kidney transplant recipients.