scholarly journals PEGylated Serp-1 Markedly Reduces Pristane-Induced Experimental Diffuse Alveolar Hemorrhage, Altering uPAR Distribution, and Macrophage Invasion

2021 ◽  
Vol 8 ◽  
Author(s):  
Qiuyun Guo ◽  
Jordan R. Yaron ◽  
John W. Wallen ◽  
Kyle F. Browder ◽  
Ryan Boyd ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Rare Complication ◽  
Diffuse Alveolar Hemorrhage ◽  
New Drugs ◽  
Lung Damage ◽  
Alveolar Hemorrhage ◽  
Clinical Complications ◽  
M1 Macrophage ◽  
Proven Efficacy ◽  
Lung Hemorrhage

Diffuse alveolar hemorrhage (DAH) is one of the most serious clinical complications of systemic lupus erythematosus (SLE). The prevalence of DAH is reported to range from 1 to 5%, but while DAH is considered a rare complication there is a reported 50–80% mortality. There is at present no proven effective treatment for DAH and the therapeutics that have been tested have significant side effects. There is a clear necessity to discover new drugs to improve outcomes in DAH. Serine protease inhibitors, serpins, regulate thrombotic and thrombolytic protease cascades. We are investigating a Myxomavirus derived immune modulating serpin, Serp-1, as a new class of immune modulating therapeutics for vasculopathy and lung hemorrhage. Serp-1 has proven efficacy in models of herpes virus-induced arterial inflammation (vasculitis) and lung hemorrhage and has also proved safe in a clinical trial in patients with unstable coronary syndromes and stent implant. Here, we examine Serp-1, both as a native secreted protein expressed by CHO cells and as a polyethylene glycol modified (PEGylated) variant (Serp-1m5), for potential therapy in DAH. DAH was induced by intraperitoneal (IP) injection of pristane in C57BL/6J (B6) mice. Mice were treated with 100 ng/g bodyweight of either Serp-1 as native 55 kDa secreted glycoprotein, or as Serp-1m5, or saline controls after inducing DAH. Treatments were repeated daily for 14 days (6 mice/group). Serp-1 partially and Serp-1m5 significantly reduced pristane-induced DAH when compared with saline as assessed by gross pathology and H&E staining (Serp-1, p = 0.2172; Serp-1m5, p = 0.0252). Both Serp-1m5 and Serp-1 treatment reduced perivascular inflammation and reduced M1 macrophage (Serp-1, p = 0.0350; Serp-1m5, p = 0.0053), hemosiderin-laden macrophage (Serp-1, p = 0.0370; Serp-1m5, p = 0.0424) invasion, and complement C5b/9 staining. Extracellular urokinase-type plasminogen activator receptor positive (uPAR+) clusters were significantly reduced (Serp-1, p = 0.0172; Serp-1m5, p = 0.0025). Serp-1m5 also increased intact uPAR+ alveoli in the lung (p = 0.0091). In conclusion, Serp-1m5 significantly reduces lung damage and hemorrhage in a pristane model of SLE DAH, providing a new potential therapeutic approach.

scholarly journals Diffuse alveolar hemorrhage: Unusual presentation of systemic lupus erythematosus

2021 ◽  
Vol 5 (1) ◽  
pp. 031-033
Author(s):  
Yassir Zajjari ◽  
Aya Sobhi ◽  
Taoufiq Aatif ◽  
Mounia Azizi ◽  
Driss Kabbaj
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Mycophenolate Mofetil ◽  
Lupus Erythematosus ◽  
Pulmonary Complication ◽  
Rare Complication ◽  
Diffuse Alveolar Hemorrhage ◽  
Alveolar Hemorrhage ◽  
Class Iii ◽  
Systemic Lupus ◽  
Aggressive Therapy

Diffuse alveolar hemorrhage (DAH) is a rare complication of systemic lupus erythematosus (SLE) and carries a high mortality. It was first described by Osler in 1904 as the most devastating pulmonary complication of SLE. We describe a case of a 23-year-old girl recently diagnosed with SLE associated by a class III nephritis treated with oral corticoids and mycophenolate mofetil who developed a Diffuse Alveolar Hemorrhage DAH a few days later. The early diagnosis and the aggressive therapy allowed us to have a favorable outcome.

scholarly journals Visceral Leishmaniasis Associated with Macrophage Activation Syndrome and Diffuse Alveolar Hemorrhage in a Lupus Patient

2018 ◽  
Vol 31 (10) ◽  
pp. 593
Author(s):  
Andreia Costa ◽  
Cármen Pais ◽  
Sofia Cerqueira ◽  
Fernando Salvador
Keyword(s):  
Amphotericin B ◽  
Lupus Erythematosus ◽  
Liposomal Amphotericin ◽  
Macrophage Activation Syndrome ◽  
Macrophage Activation ◽  
Diffuse Alveolar Hemorrhage ◽  
Alveolar Hemorrhage ◽  
Liposomal Amphotericin B ◽  
Leishmania Parasites ◽  
Activation Syndrome

Systemic lupus erythematosus is a heterogeneous and unpredictable autoimmune disease which can be complicated to approach and treat. Hemophagocytic lymphohistiocytosis and diffuse alveolar hemorrhage are rare disease complications. The authors describe a clinical case of a 32-year-old woman with lupus and fever of unknown origin. From the investigations performed, the myelogram revealed hemophagocytosis and Leishmania parasites, therefore liposomal amphotericin B was then started. In addition to directed therapy, she maintained fever that evolved with diffuse alveolar hemorrhage. The myelogram was repeated and showed that she still had hemophagocytosis but now without parasites. Corticotherapy was increased and intravenous Immunoglobulin was started, with improvement. Rituximab was started as a result of macrophage activation syndrome and diffuse alveolar hemorrhage. Months after discharge, she began once again to have sustained fever and Leishmania parasites were found again, therefore liposomal amphotericin B was started once more associated with miltefosine. She continues being followed-up as she is asymptomatic and using steroidsin weaning scheme.

scholarly journals RECURRING AND REFRACTORY DIFFUSE ALVEOLAR HEMORRHAGE AS THE FIRST MANIFESTATION OF SYSTEMIC LUPUS ERYTHEMATOSUS – CASE REPORT

2021 ◽  
Author(s):  
Laura Maria Silva de Siqueira ◽  
Douglas Squizatto Leite ◽  
João Flávio Gomes Faria ◽  
Daniela Esteves Temporim ◽  
Matheus Zanata Brufatto ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Case Report ◽  
Lupus Erythematosus ◽  
Diffuse Alveolar Hemorrhage ◽  
Alveolar Hemorrhage ◽  
Systemic Lupus ◽  
Systemic Lupus Erythematosus Case

Henrique Pereira Sampaio , Luiz Eduardo Valente , Sula Glaucia Lage Drumond Pacheco , Sean Hideo Shirata Lanças

scholarly journals Systemic lupus erythematosus and diffuse alveolar hemorrhage, etiology and novel treatment strategies

Lupus ◽  
2020 ◽  
Vol 29 (4) ◽  
pp. 355-363 ◽  
Author(s):  
N K Al-Adhoubi ◽  
J Bystrom
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Treatment Options ◽  
Unmet Need ◽  
Treatment Strategies ◽  
Diffuse Alveolar Hemorrhage ◽  
Alveolar Hemorrhage ◽  
Factor Vii ◽  
Systemic Lupus ◽  
Mesenchymal Stem Cell Therapy

Diffuse alveolar hemorrhage is a severe respiratory complication of systemic lupus erythematosus. The illness develops over hours to a few days and is the systemic lupus erythematosus-associated syndrome with highest mortality. Although no specific symptoms have been identified, a number of features are associated with diffuse alveolar hemorrhage, with a drop in blood hemoglobin the most prominent. Dyspnea, blood-stained sputum, diffuse infiltrates identified by chest imaging, elevated single breath-diffusing capacity for monoxide, thrombocytopenia and C3 hypocomplementemia are other commonly reported signs of diffuse alveolar hemorrhage. The etiology is not completely understood but many patients develop diffuse alveolar hemorrhage concomitant with lupus nephritis, suggesting immune complex-driven pathology. Biopsy studies have identified both cases with capillaritis and a bland non-inflammatory phenotype. An animal model of diffuse alveolar hemorrhage has indicated requirement of B lymphocytes and complement receptor-mediated apoptotic body phagocytosis by monocytes as part of the pathogenesis. This review will discuss considerations when diagnosing the condition and available therapies. Infections and other causes of hemorrhage have to be excluded as these require different treatment strategies. Methylprednisolone and cyclophosphamide remain the most commonly used therapies. Plasmapheresis and rituximab are other beneficial treatment options. A few studies have also considered intrapulmonary Factor VII therapy, extracorporeal membrane oxygenation and mesenchymal stem cell therapy. There is an unmet need of better definition of diffuse alveolar hemorrhages etiology and pathology for development of improved treatment strategies.

scholarly journals An uncommon cause of diffuse alveolar hemorrhage in a young male

2019 ◽  
Vol 89 (2) ◽  
Author(s):  
Anshul Mittal ◽  
Jagdish Chander Suri ◽  
Shibdas Chakrabarti ◽  
Pranav Ish
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Renal Involvement ◽  
Young Male ◽  
Diffuse Alveolar Hemorrhage ◽  
Alveolar Hemorrhage ◽  
Systemic Lupus ◽  
Threatening Condition ◽  
Life Threatening

It is uncommon for Systemic lupus erythematosus (SLE) to present with diffuse alveolar hemorrhage (DAH) as the initial presentation. To diagnose this in a young male with no renal involvement is further uncommon. We report a case of a 16-year-old boy, who presented with hemoptysis and was eventually diagnosed as DAH with underlying SLE. Treatment with steroids and immunosuppressant helped in rapid recovery from this potentially life-threatening condition. This case highlights the need of defining diagnostic criteria for SLE in patients presenting as DAH and formulating guidelines for treatment of the same, especially in absence of co-existing lupus nephritis.

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