Papel de la citocina BAFF en las enfermedades autoinmunes: rol fisiopatológico y estrategias terapéuticas

Ospina, Fabio E.; Betancur, Juan Felipe; Suso, Juan Pablo; Muñoz-Buitrón, Evelyn; Cañas, Carlos A.; Tobón, Gabriel J.

doi:10.1016/j.rcreu.2016.06.003

Cited by 2 publications

(4 citation statements)

References 118 publications

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“…Second, our results are limited to differential cytokine protein expression in patients with PolyA, and further studies using transcriptional expression measurement are warranted, because several cell populations may produce measured plasma cytokines. Third, it is considered that after 6 months of BCDT some patients present B-cells repopulation as an effect of the increase in BAFF levels (6), which may bias cytokine concentration. Nonetheless, B-cell numbers in most of our samples (8 out of 11) were assessed by flow cytometry in a previous study (45), and we observed that 5 out of 8 available patients did not have B-cell repopulation (>5000 cells/ mL) ( Figures S1 and S2), suggesting that this was not an important variable in our study.…”

Section: Discussionmentioning

confidence: 99%

“…BAFF (B-cell activating factor, also known as B lymphocyte stimulator, BLyS) and APRIL (aproliferation inducing ligand) are some of the most important cytokines influencing development and survival of B-cells, and, in turn, play a major role in ADs pathophysiology (6). Nonetheless, several other cytokines are secreted or influence the growth and function of B-cells.…”

Section: Introductionmentioning

confidence: 99%

“…However, when B-cell Ab production capability was eliminated, mice still developed SLE features, which suggests an Abindependent role (32). Evidence in humans has shown that BCDT using belimumab, a monoclonal Ab targeted at soluble BAFF that impairs B-cell development and survival (6), is effective as SLE treatment (33,34). However, RTX showed an overall poor efficacy for SLE, although some patients showed improvement (35,36).…”

Section: Introductionmentioning

confidence: 99%

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Comparison of Plasma Cytokine Levels before and after Treatment with Rituximab in Patients with Rheumatoid Arthritis and Systemic Lupus Erythematosus-Associated Polyautoimmunity

Barahona-Correa¹,

Cortés²,

Uribe³

et al. 2018

UNIV.MED.

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Introduction: Coexistence of more than one autoimmune disease (AD) in a single patient is known as polyautoimmunity, and may be seen in up to 35% of patients with ADs. The elimination of B-cells using Rituximab (RTX) improves clinical status in different ADs. The role of cytokine production by B-cells is unclear in systemic lupus erythematosus (SLE) and polyautoimmunity. Methods: As an exploratory study, plasma from 11 patients with either rheumatoid arthritis (RA) or SLE-associated polyautoimmunity was assessed prior and 6 months after therapy with RTX. Eight healthy individuals were used as controls. Cytokine levels were measured using ELISA (IFN-α and TGF-β1) or Cytometric Bead Array (TNF-α, IL-1β, IL-6, IL-8, IL-10, and IL-12p70). Results: Prior to RTX, IL-6 was only elevated in RA and IL-8 was elevated in both RA and SLE-associated polyautoimmunity, compared with controls. After RTX, significant decreases of IL-6 in RA and IL-8 in SLE-associated polyautoimmunity were observed. Levels of other cytokines measured were either similar (IFN-α, TGF β1) or below the detection limit (TNF-α, IL-1β, IL-10, IL-12p70) for both patients and controls. Conclusion:Our data highlight the importance of B-cell cytokine secretion in RA and SLE-associated polyautoimmunity, and suggest a differential role in each pathology. A significant increase of IL-8 prior to RTX in both groups, and a significant decrease after therapy only in SLE-associated polyautoimmunity support the potential of IL-8 as a therapeutic target. The heterogeneity of the polyautoimmunity patient population highlights the importance of the selection of specific subsets in future research.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Comparison of Plasma Cytokine Levels before and after Treatment with Rituximab in Patients with Rheumatoid Arthritis and Systemic Lupus Erythematosus-Associated Polyautoimmunity

Barahona-Correa¹,

Cortés²,

Uribe³

et al. 2018

UNIV.MED.

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“…These antibodies can be produced by loss of central or peripheral tolerance, by altered expression of PLA2R in podocytes, sensitising them to the damaging action of anti-PLA2Rs. It is di cult to verify whether these mechanisms are triggered by RA itself, but the cytokine TNF-like weak inducer of apoptosis (TWEAK) has been associated with RA and is found in high concentrations in synovial tissue 7 . This proin ammatory molecule increases the expression of PLA2R in podocytes, sensitising them to the damaging action of anti-PLA2Rs 8 .…”

Section: Case Presentationmentioning

confidence: 99%

Rheumatoid Arthritis and Pla2r-associated Mebranous Nephropathy . Cause or Coincidence?

Perea-Ortega,

Muñoz-Sánchez,

León-Fradejas

et al. 2024

Preprint

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Background: Rheumatoid arthritis affects 0.5% of adults in our country. It is an inflammatory disease that predominantly affects the joints causing destruction of the articular cartilage. Approximately 50% of patients present with extra-articular manifestations. Renal involvement is relatively frequent and clinically significant because it worsens the course and mortality of the primary disease. The histological renal damage observed in such patients includes a wide variety of entities and histological patterns with both glomerular and tubulointerstitial involvement, with secondary membranous nephropathy being one of the most common. Coexistence with primary membranous nephropathy is rare. Case Presentation: A 46-year-old man recently diagnosed with rheumatoid arthritis was referred to the nephrology department for deterioration of renal function and subnephrotic proteinuria. The autoimmune study showed positive anti-PLA2R. Due to the unusual association between both entities, it was decided to perform a renal biopsy which showed abundant spikes. The immunofluorescence study showed contiguous parietal IgG positivity (3+). Immunohistochemistry showed positive granular IgG4, confirming the diagnosis of PLA2R-associated membranous nephropathy. Conclusions: Membranous nephropathy is one of the most common causes of nephrotic syndrome in adults. The determination of anti-PLA2R has been a great advance in the rapid differential diagnosis of MN. In recent years, new target antigens associated with certain underlying pathologies have been discovered. However, PLA2R is not associated with any disease or exposure and therefore remains the antigen responsible for 80% of primary NMs. Anti-PLA2R antibodies can be produced by loss of central or peripheral tolerance. Whether these mechanisms are triggered by rheumatoid arthritis itself is difficult to prove. The cytokine TNF-like weak inducer of apoptosis (TWEAK) has been associated with rheumatoid arthritis. This proinflammatory molecule increases the expression of PLA2R in podocytes, sensitising them to the damaging action of anti-PLA2Rs, which could justify a causal relationship between the two pathologies. Treatment should be tailored to the individual risk profile for progression. Rituximab could be an optimal option for both entities.

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Papel de la citocina BAFF en las enfermedades autoinmunes: rol fisiopatológico y estrategias terapéuticas

Cited by 2 publications

References 118 publications

Comparison of Plasma Cytokine Levels before and after Treatment with Rituximab in Patients with Rheumatoid Arthritis and Systemic Lupus Erythematosus-Associated Polyautoimmunity

Comparison of Plasma Cytokine Levels before and after Treatment with Rituximab in Patients with Rheumatoid Arthritis and Systemic Lupus Erythematosus-Associated Polyautoimmunity

Rheumatoid Arthritis and Pla2r-associated Mebranous Nephropathy . Cause or Coincidence?

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