Iván Posso-Osorio

Autoimmune diseases and their relation with immunological, neurological and endocrinological axes

The immune response is complex, multifactorial, individualized and often unpredictable. There are multiple interconnected systems that allow a balance between physiological autoreactive processes and pathological autoimmunity with consequent organ-specific or systemic autoimmune disease. Based on the concept of the autoimmunity mosaic, up to 50% of autoimmune disorders do not have a clear etiological factor. In order to achieve a clear understanding of the different systems that influence the development of autoimmune diseases, the clinical auto-immunologist needs a dynamic and comprehensive vision of all interconnected pathways that maintain a precise balance in the organism. This has been and will remain a challenge. Understanding the different pathophysiological processes of these diseases will be the basis for predicting different clinical spectra and has the potential to offer innovative therapeutic approaches. This paper offers a practical overview of the bidirectional communication between the immune and endocrine system and the influence this has on the development of autoimmune diseases.

Sequential rituximab and omalizumab for the treatment of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome (CSS), is a small vessel vasculitis associated with eosinophilia and asthma. Clinical manifestations commonly seen in patients presenting with EGPA range from upper airway and lung involvement to neurological, cardiac, cutaneous, and renal manifestations. Treatment for severe presentations includes steroids, cyclophosphamide, plasmapheresis, and recently, rituximab. Rituximab is associated with a good response in the treatment of vasculitis, but a variable response for the control of allergic symptoms. Here, we report a 16-year-old female patient with severe EGPA (gastrointestinal and cutaneous vasculitis, rhinitis and asthma) refractory to conventional treatment. She was treated with rituximab, which enabled rapid control of the vasculitis component of the disease, but there was no response to rhinitis and asthma. Additionally, she developed severe bronchospasm during rituximab infusion. Sequential rituximab and omalizumab were initiated, leading to remission of all manifestations of vasculitis, rhinitis, and asthma, in addition to bronchospasm related to rituximab infusion.

Profile of BAFF and its receptors’ expression in lupus nephritis is associated with pathological classes

Background/Objective B-cell activating factor (BAFF) plays an important role in the pathogenesis of systemic lupus erythematosus. However, the role of BAFF in lupus nephritis (LN) is not understood. Our aim was to evaluate the expression of BAFF and its three receptors in renal biopsy samples from patients with LN and investigate a relationship with pathological class. Methods We conducted a prospective descriptive study (2011–2014) on 52 kidney biopsy samples from patients with LN. Immunohistochemistry for BAFF, its receptors (transmembrane activator and calcium modulator and cyclophilin ligand interaction (TACI), protein maturation of B cells (BCMA), and BAFF-receptor (BAFF-R)), and CD20 expression was performed. Samples were scored according to the percentage of cells with positive expression. Results In class II LN, BAFF-R and TACI were not expressed, whereas BCMA and BAFF were lowly expressed in the interstitial inflammatory infiltrates. Proliferative class III/IV had elevated BAFF expression in the glomeruli, and TACI was expressed in interstitial inflammatory infiltrates and the glomeruli. Interestingly, the class IV cases with vasculopathy (n = 4) had endothelial BAFF expression, which was not visible in thrombotic microangiopathy (n = 4). Class V was characterized by low BAFF expression in interstitial inflammatory infiltrates and by BAFF, TACI, and BCMA expression in the glomeruli. BAFF expression was associated with inflammatory scores and CD20 positive infiltrates, mainly in class IV. Conclusions Expression patterns of BAFF and its receptors differ according to LN class. Our study provides evidence that BAFF could be used as a routine marker in LN biopsies and to determine which patients will benefit from anti-BAFF therapy.

Cytokine markers of B lymphocytes in minor salivary gland infiltrates in Sjögren's syndrome

Sjögrens syndrome (SS) is a chronic autoimmune disorder characterised by the clinical presence of sicca syndrome. SS compromises the dysfunction of exocrine glands due to the presence of focal, mononuclear cell infiltrates that surround the ducts and replace the secretory units. Abnormal expression of different cytokines and chemokines such as B-cell activating factor, CXC Motif Chemokine Ligand 13, interleukin 6 (IL-6), IL-22, and FMS-like tyrosine kinase 3 ligand as well as that of their corresponding receptors has been implicated in the inflammatory process. The severity of glandular infiltration has been suggested to be associated with the presence of extra-glandular systemic manifestations, contributing to a clinical spectrum of the most severe disease. This review describes several cytokines and chemokines associated with B lymphocytes expressed in the minor salivary gland, their chemical structures, and their roles in SS as possible early predictors of lymphoma development and disease progression.

Acquired haemophilia A secondary to systemic lupus erythematosus: favourable response to rituximab

Abstract Acquired haemophilia A (AHA) is a rare bleeding disorder and the main cause of coagulation factor deficiency. AHA is caused by the development of antibodies, also known as inhibitors, against coagulation factor VIII (FVIII) that neutralize their activity which, in more serious forms, results in bleeding. This article describes a case of a 54-year-old woman with a diagnosis of Systemic Lupus Erythematosus (SLE) occurring for the past 12 years, who presented to the clinic because of multiple spontaneous ecchymoses. Clinical findings included prolonged thromboplastin time (aPTT), absence of factor VIII activity, high factor VIII inhibitor levels (208 BU/mL), and crossed PTT with no evidence of correction after serial dilutions. AHA was considered secondary to SLE, and due to the severity of the ecchymoses, the patient required Feiba VH®, methylprednisolone and cyclophosphamide therapy, although no adequate response was achieved. As a result, four doses of weekly rituximab therapy were given and coagulation profile standardization and complete clinical improvement were achieved.

Neutrophil CD64 expression, procalcitonin and presepsin are useful to differentiate infections from flares in SLE patients with SIRS

Background/Objective Differentiating systemic lupus erythematosus (SLE) activity from infections in febrile patients is difficult because of similar initial clinical presentation. The aim of this study is to evaluate the usefulness of a number of biomarkers for differentiating infections from activity in SLE patients admitted with systemic inflammatory response (SIRS). Methods Patients with SLE and SIRS admitted to the emergency room were included in this study. Measurements of different markers including procalcitonin, neutrophil CD64 expression and presepsin, were performed. Infection was considered present when positive cultures and/or polymerase chain reaction were obtained. Sensitivity and specificity were calculated for all biomarkers. Results Twenty-seven patients were admitted, 23 women (82.5%), mean age 33.2 years. An infectious disease was confirmed in 12 cases. Markers for SLE activity including anti-DNA titers by IIF (p = 0.041) and enzyme-linked immunosorbent assay (p = 0.009) were used for differentiating SLE flares from infection. On the contrary, increased procalcitonin (p = 0.047), neutrophil CD64 expression by flow cytometry (p = 0.037) and presepsin (p = 0.037) levels were observed in infected SLE patients. Conclusions High neutrophil CD64 expression, presepsin and procalcitonin levels are useful to differentiate infections from activity in SLE patients. In most cases, a positive bioscore that includes these three markers demonstrate the presence of an infectious disease.

Hepatic infiltration by silicone in a patient With ASIA syndrome

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) is frequently characterized by myalgias, myositis, arthralgia, neurological manifestations, fever, dry mouth, and cognitive alterations. In the range of clinical conditions related to ASIA syndrome, siliconosis after breast implants has been reported. Here, we report a case of hepatic infiltration by silicone in a patient with ASIA syndrome.