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Scientific Reports Aug 2023Antibody phage display is a key tool for the development of monoclonal antibodies against various targets. However, the development of anti-peptide antibodies is a...
Antibody phage display is a key tool for the development of monoclonal antibodies against various targets. However, the development of anti-peptide antibodies is a challenging process due to the small size of peptides for binding. This makes anchoring of peptides a preferred approach for panning experiments. A common approach is by using streptavidin as the anchor protein to present biotinylated peptides for panning. Here, we propose the use of recombinant expression of the target peptide and an immunogenic protein as a fusion for panning. The peptide inhibitor of trans-endothelial migration (PEPITEM) peptide sequence was fused to the Mycobacterium tuberculosis (Mtb) α-crystalline (AC) as an anchor protein. The panning process was carried out by subtractive selection of the antibody library against the AC protein first, followed by binding to the library to PEPITEM fused AC (PEPI-AC). A unique monoclonal scFv antibodies with good specificity were identified. In conclusion, the use of an alternative anchor protein to present the peptide sequence coupled with subtractive panning allows for the identification of unique monoclonal antibodies against a peptide target.
Topics: Humans; Antibodies, Monoclonal; Amino Acid Sequence; Single-Chain Antibodies; Cell Surface Display Techniques; Polyarteritis Nodosa; Bacteriophages
PubMed: 37604859
DOI: 10.1038/s41598-023-40630-7 -
Clinical Case Reports Aug 2023Heart failure due to ANCA-negative vasculitis, is a rare potentially life-threatening manifestation of ANCA vasculitis. Therefore, physicians must always pay attention...
KEY CLINICAL MESSAGE
Heart failure due to ANCA-negative vasculitis, is a rare potentially life-threatening manifestation of ANCA vasculitis. Therefore, physicians must always pay attention to this manifestation for proper disease diagnosis and treatment.
ABSTRACT
Less than 10% of primary vasculitides cause cardiac dysfunction, with Takayasu's arteritis, polyarteritis nodosa, and eosinophilic granulomatosis with polyangiitis being the most common cases. However, any cardiac tissue can be affected by ANCA vasculitis. We present a case of heart failure with reduced ventricular ejection fraction due to ANCA negative-vasculitis.
PubMed: 37546160
DOI: 10.1002/ccr3.7749 -
Kidney Diseases (Basel, Switzerland) May 2023Autoinflammatory diseases (AIDs) were first proposed 20 years ago and caused by dysregulation of the innate immune system, leading to episodes of systemic inflammation.... (Review)
Review
BACKGROUND
Autoinflammatory diseases (AIDs) were first proposed 20 years ago and caused by dysregulation of the innate immune system, leading to episodes of systemic inflammation. Advances in next-generation sequencing and biological technology have resulted in the identification of new monogenic diseases and the corresponding signaling pathways that may guide us in targeted therapy. The kidney is a major target organ of various inflammatory processes.
SUMMARY
During systemic inflammation, increased pro-inflammatory cytokines, such as IL-6, IL-1β, and TNF, lead to over-transcription and release of acute phase reactant serum amyloid A (SAA). Sustained high SAA levels promote a cascade of pathophysiological events, including protein misfolding, protein fragmentation, and aggregation into highly ordered amyloid fibrils. Amyloid fibril deposition in the kidney cause progressive glomerular and vascular damage. Renal AA amyloidosis is a common and severe complication of AIDs, including familial Mediterranean fever, cryopyrin-associated periodic syndromes, TNF receptor-associated periodic fever syndrome, mevalonate kinase deficiency/hyper-IgD and periodic fever syndrome, and deficiency of adenosine deaminase 2. Amyloidosis may even be the first clinical manifestation in some patients, presenting with asymptomatic proteinuria, nephritic syndrome, progressive renal insufficiency, or end-stage kidney disease. In addition, major dysregulated pathways in different AIDs lead to endogenous inflammation, which is due to direct endothelial cytotoxicity caused by IL-1β, type I interferon, or possibly immune complexes. The kidney is frequently affected by various vasculitis, and kidney involvement is a major determinant of treatment options and outcomes. The renal vasculitis involved in AIDs includes renal artery Takayasu vasculitis, polyarteritis nodosa, and IgA vasculitis. Moreover, other kidney diseases, such as glomerulonephritis, lupus nephritis, and renal tubular dysfunction, were also reported in AIDs.
KEY MESSAGES
Kidney manifestations can be a coexisting disease seen with AIDs. They may also be one of the characteristics of AIDs. Clinicians should be aware of the possibility that amyloidosis, vasculitis, or other kidney diseases may be associated with AIDs in order to make appropriate diagnosis and treatment. Kidney biopsy may be of great significance. Biologics, which switch off the underlying cytokine-mediated inflammatory process, have the potential to restore organ damage and improve the outcome in the very early stage of the disease.
PubMed: 37497206
DOI: 10.1159/000529917 -
The Pan African Medical Journal 2023Intracardiac thrombus is an exceptional complication revealing Behçet's disease. We here report the case of a 48-year-old patient admitted with stroke. Clinical...
Intracardiac thrombus is an exceptional complication revealing Behçet's disease. We here report the case of a 48-year-old patient admitted with stroke. Clinical examination showed recurrent oral aphthous ulcers. Cardiovascular examination was normal, magnetic resonance imaging (MRI) objectified left posterior parietal stroke. Transthoracic echocardiogram showed totally thrombosed apical aneurysm measuring 42mm/36mm. Total-body computed tomography (CT) scan was performed to detect other abnormalities. It was normal apart from cardiac involvement. The diagnosis of Behçet's disease was made based on oral aphthous ulcers, polyarteritis nodosa and thrombosed left ventricular aneurysm. Outcome was favorable under medical treatment combining anticoagulants, corticosteroids and immunosuppression.
Topics: Humans; Middle Aged; Behcet Syndrome; Stomatitis, Aphthous; Thrombosis; Heart Aneurysm; Stroke
PubMed: 37484586
DOI: 10.11604/pamj.2023.44.200.12844 -
Medicine Jul 2023We report the case of a patient who initially presented with peripheral neuropathy and myositis without typical organ involvement, such as the kidneys, skin, or...
RATIONALE
We report the case of a patient who initially presented with peripheral neuropathy and myositis without typical organ involvement, such as the kidneys, skin, or gastrointestinal system, but was ultimately diagnosed with polyarteritis nodosa (PAN).
PATIENT CONCERNS
A 62-year-old man presented with radicular pain in his right lower extremity. One week later, he complained of right ankle motor weakness and pain in the right posterior thigh, which led to admission. After 6 weeks of hospitalization, he newly experienced pain in his right testicle and anterior thigh.
DIAGNOSIS
The patient was initially diagnosed with polymyositis combined with sciatic neuropathy using magnetic resonance imaging, electrodiagnostic tests, and muscle biopsy. However, with the emergence of other systemic symptoms such as testicular pain, vasculitis was suspected, and the patient was reclassified as PAN using the 2007 European Medicines Agency algorithm and the American College of Rheumatology criteria.
INTERVENTIONS
The patient was treated with glucocorticoids for more than 6 months, and antiviral medication was prescribed to prevent hepatitis B virus reactivation.
OUTCOMES
The patient's radicular pain and pain in the right anterior and posterior thighs and testicle improved, and there were no signs of recurrence.
LESSONS
In patients presenting with radicular and focal muscle pain, it is crucial to consider the potential for PAN, as observed in this case report.
Topics: Male; Humans; Middle Aged; Polyarteritis Nodosa; Peripheral Nervous System Diseases; Polymyositis; Testis; Muscle Weakness; Pain
PubMed: 37478214
DOI: 10.1097/MD.0000000000034335 -
Journal of Rheumatic Diseases Oct 2022Deficiency of adenosine deaminase 2 (DADA2) is an autoinflammatory disease caused by pathogenic variants of the gene and has similar clinical features to polyarteritis...
Deficiency of adenosine deaminase 2 (DADA2) is an autoinflammatory disease caused by pathogenic variants of the gene and has similar clinical features to polyarteritis nodosa (PAN). We, herein, report a case of DADA2 in Korea that was diagnosed in a patient with childhood-onset PAN. The patient had a truncal ataxia and facial palsy caused by thalamic infarction at 34 months of age. Livedo reticularis with Raynaud phenomenon and abdominal pain with fever were followed. Radiologic examination showed multiple infarctions in brain and kidney. She was diagnosed with PAN using skin biopsy and angiography. She had severe hemorrhagic strokes despite medical treatments. Her disease activity was controlled after adding a tumor necrosis factor-α inhibitor. Molecular analysis revealed compound heterozygous pathogenic variants of gene. This is the first case of DADA2 in Korea. Genetic analysis for gene should be considered in patients with childhood-onset PAN.
PubMed: 37476427
DOI: 10.4078/jrd.21.0046 -
Medicina (Kaunas, Lithuania) Jun 2023Classic polyarteritis nodosa (PAN) is a vasculitis with systemic manifestations that is characterized by inflammatory and necrotizing lesions affecting medium and small... (Review)
Review
Classic polyarteritis nodosa (PAN) is a vasculitis with systemic manifestations that is characterized by inflammatory and necrotizing lesions affecting medium and small muscular arteries, most frequently at the bifurcation of the vessels. These lesions lead to the formation of microaneurysms, hemorrhaging ruptured aneurysms, thrombosis, and, consequently, ischemia or organ infarction. : We present a complex clinical case of a patient with a late diagnosis of polyarteritis nodosa with multiorgan involvement. : The 44-year-old patient, in an urban environment, presented on her own in the emergency room for acute ischemia phenomena and forearm and right-hand compartment syndrome, requiring surgical decompression in the Plastic Surgery Clinic. : Significant inflammatory syndrome is noted, alongside severe normocytic hypochromic iron deficiency anemia, nitrogen retention syndrome, hyperkalemia, hepatic syndrome, and immunological disturbances: absence of cANCA, pANCA, anti Scl 70 Ac, antinuclear Ac, and anti dDNA Ac, as well as a low C3 fraction of the plasmatic complement system. The morphological aspect described in the right-hand skin biopsy correlated with the clinical data supports the diagnosis of PAN. : The viral form of PAN seems to be individualized as a distinct entity, requiring early, aggressive medication.
Topics: Humans; Female; Adult; Polyarteritis Nodosa; Arteries; Biopsy; Antibodies, Antineutrophil Cytoplasmic
PubMed: 37374366
DOI: 10.3390/medicina59061162 -
Journal of Clinical Rheumatology :... Dec 2023
Topics: Humans; Gangrene; Polyarteritis Nodosa
PubMed: 37337335
DOI: 10.1097/RHU.0000000000001998 -
Rheumatology Advances in Practice 2023Cutaneous polyarteritis nodosa (CPAN) is a distinct clinical entity represented by a chronic, relapsing, benign course, with rare systemic involvement. Treatment is with...
OBJECTIVE
Cutaneous polyarteritis nodosa (CPAN) is a distinct clinical entity represented by a chronic, relapsing, benign course, with rare systemic involvement. Treatment is with CSs, CYC or other conventional synthetic DMARDs (csDMARDs). In this case series, we aimed to share our varied clinical experience of successfully treating patients with CPAN, with tofacitinib in a refractory/relapsing course or as upfront monotherapy without CSs/csDMARDs.
METHODS
We report this retrospective case series managed at our rheumatology centre in Bangalore from 2019 to 2022. Four patients identified as CPAN on biopsy were able to achieve disease-free remission with tofacitinib as part of their treatment, with no relapse on further follow-up. Our patients presented with subcutaneous nodules and cutaneous ulcers. After systemic evaluation, all the patients underwent skin biopsy, which showed fibrinoid necrosis in the vessel walls of the dermis, with a histopathological impression of CPAN. They were initially treated with a conventional approach of CSs with/without csDMARDs. On experiencing a refractory/relapsing course, tofacitinib was tried in all the patients as either CS sparing or upfront monotherapy without concomitant csDMARDs.
RESULTS
Use of tofacitinib resulted in improvement of ulcers and paraesthesia and in gradual healing of skin lesions, albeit with scarring, with no further recurrence or relapse over a follow-up period of 6 months for all the patients. The therapeutic effect of tofacitinib was consistent when used either as CS sparing or as upfront monotherapy, thereby proving the drug to be a promising option that warrants larger trials in future to treat the subset of patients with established CPAN.
CONCLUSION
Tofacitinib could be used for disease-free remission as monotherapy for CPAN either upfront or as CS sparing, even without concomitant csDMARDs, in those patients who are dependent on CSs or multiple DMARDs.
PubMed: 37325248
DOI: 10.1093/rap/rkad049 -
Surgical Case Reports Jun 2023Polyarteritis nodsa (PAN) is a rare disease characterized by acute focal inflammatory damage to small and medium arteries. PAN complicated by ruptured aneurysm is an...
BACKGROUND
Polyarteritis nodsa (PAN) is a rare disease characterized by acute focal inflammatory damage to small and medium arteries. PAN complicated by ruptured aneurysm is an infrequent presentation with the most affected arteries being the renal and mesenteric arteries.
CASE PRESENTATION
A 76-year-old female presented with a low-grade fever, generalized body aches, and abdominal pain. Investigation revealed intraperitoneal bleeding secondary to a ruptured and actively bleeding right omental artery aneurysm. Clinical manifestation, angiography and histology were consistent with PAN. Laparotomy was performed for stabilization and resection of the bleeding aneurysm followed by post operative steroids and cyclophosphamide. Patient was discharged in a stable condition. We reviewed seven cases found in the literature of omental artery aneurysm and rupture. Four cases were proceeded with laparotomy and aneurysm resection while three cases were proceeded with a less invasive approach of arterial embolization.
CONCLUSIONS
Omental artery aneurysm is a rare occurrence with even fewer reported cases associated with PAN. Of the seven reported cases, all patients were treated with a surgical intervention. In addition, PAN patients should be treated post-operatively with a course of steroids and cyclophosphamide.
PubMed: 37266725
DOI: 10.1186/s40792-023-01675-y