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Journal of Rheumatic Diseases Jul 2024To report the frequency of selected autoantibodies and their associations with clinical features in Arab children with monogenic lupus.
OBJECTIVE
To report the frequency of selected autoantibodies and their associations with clinical features in Arab children with monogenic lupus.
METHODS
This study was retrospective single-center study of genetically confirmed monogenic lupus cases at childhood lupus clinic at King Faisal Specialist Hospital and Research Center, from June 1997 to July 2022. We excluded familial lupus without genetic testing and patients with insufficient data. Collected data comprised clinical and laboratory findings, including the autoantibody profile, which included the anti-double-stranded DNA (anti-dsDNA), anti-Smith, anti-Sjögren's-syndrome-related antigen A (anti-SSA), anti-Sjögren's-syndrome-related antigen B (anti-SSB), and antiphospholipid (APL) antibodies. Also, disease activity and accrual disease damage were collected at the last follow-up visit.
RESULTS
This study enrolled 27 Arab patients (14 males) with a median age of 11 years (interquartile range 8.0~16 years), with 63% having early-onset disease. The consanguinity rate and family history of lupus were high (74.1% and 55.6%, respectively). The most frequent clinical features were hematological (96.3%), fever (81.5%), mucocutaneous lesions (85.2%), and renal (66.7%). The frequency of the APL antibodies was 59.3%, anti-dsDNA was 55.6%, and anti-Smith and anti-SSA were 48.2% and 44.4%, respectively. Moreover, dsDNA antibodies were significantly associated with musculoskeletal complaints (p<0.05). Likewise, both anti-Smith and anti-SSA antibodies were linked to failure to thrive and recurrent infections in the univariate analysis (p<0.05).
CONCLUSION
Our study reveals autoantibody frequencies and their association with clinical and prognostic in a substantial monogenic lupus cohort. Distinct clinical manifestations and prognosis association with certain autoantibodies support the idea that monogenic lupus is a distinctive form of lupus. Larger studies needed to validate these findings.
PubMed: 38957362
DOI: 10.4078/jrd.2023.0065 -
Journal of Rheumatic Diseases Jul 2024In this study, the association between the monocyte-to-high-density lipoprotein cholesterol ratio (MHR) at diagnosis and poor outcomes of atherosclerosis-related...
The monocyte-to-high-density lipoprotein-cholesterol ratio at diagnosis is associated with cerebrovascular accident during follow-up in patients with antineutrophil cytoplasmic antibody-associated vasculitis.
OBJECTIVE
In this study, the association between the monocyte-to-high-density lipoprotein cholesterol ratio (MHR) at diagnosis and poor outcomes of atherosclerosis-related antineutrophil cytoplasmic antibody-associated vasculitis (AAV) during follow-up in patients with AAV was investigated.
METHODS
This retrospective study included 138 patients diagnosed with AAV. Their comprehensive medical records were meticulously reviewed. All-cause mortality, cerebrovascular accident (CVA), and acute coronary syndrome (ACS) were evaluated as atherosclerosis-related poor outcomes of AAV. MHR was obtained by dividing monocyte counts (/mm3) by high-density lipoprotein cholesterol (mg/dL) levels.
RESULTS
The median age of the 138 patients was 58.3 years with 44 being male (31.9%). Among the 138 patients, 11 (8.0%) died, and 11 (8.0%) and 9 (6.5%) had CVA, and ACS, respectively. MHR at diagnosis was significantly correlated with the Birmingham vasculitis activity score, erythrocyte sedimentation rate, and C-reactive protein at diagnosis. Among the three poor outcomes of AAV, only CVA during follow-up was significantly associated with MHR at diagnosis, and thus, only CVA was considered an atherosclerosis-related poor outcome of AAV. In the multivariable Cox hazards model analysis, MHR (hazard ratio [HR] 1.195) and serum albumin (HR 0.203) at diagnosis were independently associated with CVA during follow-up. Additionally, patients with MHR at diagnosis ≥3.0 exhibited a significantly higher risk for CVA and lower cumulative CVA-free survival rate than those with MHR at diagnosis <3.0.
CONCLUSION
This study is the first to demonstrate clinical implications of MHR suggesting that MHR at diagnosis is significantly and independently associated with CVA during follow-up in patients with AAV.
PubMed: 38957360
DOI: 10.4078/jrd.2024.0001 -
Frontiers in Oncology 2024Immune checkpoint inhibitors (ICIs) demonstrate unique advantages in the treatment of lung cancer and are widely used in the era of immunotherapy. However, ICIs can...
Immune checkpoint inhibitors (ICIs) demonstrate unique advantages in the treatment of lung cancer and are widely used in the era of immunotherapy. However, ICIs can cause adverse reactions. Hematological toxicities induced by immunotherapy are relatively rare. Agranulocytosis, a rare hematologic adverse event associated with immune checkpoint inhibitors, has received limited attention in terms of treatment and patient demographics. Herein, we report the case of a 68-year-old male with non-small cell lung cancer(NSCLC) who received two cycles of programmed cell death-1 (PD-1) antibody sintilimab immunotherapy combined with albumin-bound paclitaxel and carboplatin chemotherapy and one cycle of sintilimab monotherapy. He was diagnosed with grade 4 neutropenia and sepsis (with symptoms of fever and chills) after the first two cycles of treatment. Teicoplanin was promptly initiated as antimicrobial therapy. The patient presented with sudden high fever and developed agranulocytosis on the day of the third cycle of treatment initiation, characterized by an absolute neutrophil count of 0.0×10/L. The patient was treated with granulocyte colony-stimulating factor but did not show improvement. He was then treated with corticosteroids, and absolute neutrophil counts gradually returned to normal levels. To the best of our knowledge, this is the first reported case of sintilimab-induced agranulocytosis in a patient with NSCLC. Sintilimab-induced severe neutropenia or agranulocytosis is a rare side effect that should be distinguished from chemotherapy-induced neutropenia and treated promptly with appropriate therapies; otherwise, the condition may worsen.
PubMed: 38957321
DOI: 10.3389/fonc.2024.1415748 -
Cureus Jun 2024Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis, is an anti-neutrophilic cytoplasmic autoantibody (ANCA)-associated small-vessel...
Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis, is an anti-neutrophilic cytoplasmic autoantibody (ANCA)-associated small-vessel vasculitis. Typically, it causes upper and lower respiratory tract necrotizing granulomatous inflammation and necrotizing glomerulonephritis. The diagnosis is made through clinical symptoms, positive antibody testing, imaging, and kidney biopsy. We describe the case of a man in his 60s who presented with multiple complications of GPA including rapidly progressive renal failure requiring dialysis, diffuse alveolar hemorrhage, acute respiratory distress syndrome (ARDS), circulatory shock, submassive pulmonary embolism, and biventricular and dilated cardiomyopathy.
PubMed: 38957259
DOI: 10.7759/cureus.61529 -
Cureus Jun 2024Acute mesenteric ischemia is a critical condition marked by a sudden loss of blood supply to the intestines, often leading to rapid tissue necrosis and severe clinical...
Acute mesenteric ischemia is a critical condition marked by a sudden loss of blood supply to the intestines, often leading to rapid tissue necrosis and severe clinical outcomes if untreated. In the context of hypogammaglobulinemia, an immunodeficiency characterized by decreased levels of immunoglobulins, this vascular emergency becomes even more daunting. Hypogammaglobulinemia can impair the immune system's response to both infection and ischemic injury, intensifying the severity of intestinal damage. This report describes the case of a 52-year-old female with hypogammaglobulinemia who presented with severe abdominal pain. Surgical exploration revealed 100 cm of necrotic small bowel extending from 150 cm distal to the ligament of Treitz to within 10 cm of the ileocecal valve. The necrotic section was surgically removed, and primary anastomosis was performed. This instance highlights the significant impact of immunodeficiency on the progression and management of acute mesenteric ischemia, demonstrating the critical need for early intervention and tailored management strategies, especially in immunocompromised patients, to prevent severe outcomes. The case illuminates the importance of recognizing immunodeficiency as a complicating factor in acute gastrointestinal emergencies, stressing the necessity for prompt and effective medical and surgical interventions to improve prognosis and patient outcomes in complex clinical scenarios.
PubMed: 38957256
DOI: 10.7759/cureus.61531 -
Cureus Jun 2024Background Subclinical hypothyroidism (SCH) is characterized by elevated thyroid-stimulating hormone (TSH) levels, while thyroid hormones (free thyroxine (T4) and free...
Serum Vitamin B12 and Holotranscobalamin Levels in Subclinical Hypothyroid Patients in Relation to Thyroid-Stimulating Hormone (TSH) Levels and the Positivity of Anti-thyroid Peroxidase Antibodies: A Case-Control Study.
Background Subclinical hypothyroidism (SCH) is characterized by elevated thyroid-stimulating hormone (TSH) levels, while thyroid hormones (free thyroxine (T4) and free triiodothyronine (T3)) remain within the reference ranges. Vitamin B12 (cobalamin) deficiency is common in patients with autoimmune disorders, including autoimmune hypothyroidism. The study was aimed at evaluating serum vitamin B12 levels and holotranscobalamin (HoloTC) levels in SCH patients and ascertaining their association with a risky level of TSH and the positivity of anti-thyroid peroxidase (anti-TPO) antibodies. Methodology A case-control study was conducted at Azadi Teaching Hospital, Duhok, a city in the Kurdistan region of Iraq, involving 153 participants, including 72 newly diagnosed SCH patients and 81 healthy controls. Serum levels of vitamin B12, HoloTC, TSH, free T4, free T3, and anti-TPO antibodies were measured based on different principles. Results The mean age of patients with SCH was 32.87±8.7 years, with predominantly females comprising 75% and 77.8% being less than 40 years of age. Moreover, the mean levels of serum TSH (6.96±2.68 µIU/L), anti-TPO antibodies (53.31±81.32 IU/ml), and HoloTC (41.93±19.42 pmol/l) were significantly higher in patients with SCH compared to healthy control participants (p < 0.05), whereas there was a non-significantly higher level of vitamin B12(320.72±98.42 pg/ml) among SCH patients compared to healthy control participants (p = 0.220). The mean levels of vitamin B12 (345.33±103.22 pg/ml) and HoloTC (40.14±18.16 pmol/l) were insignificantly lower in SCH patients with TSH levels more than 7 µIU/L (p > 0.05), as well as the mean levels of vitamin B12 (308.82±96.12 pg/ml) and HoloTC (41.14±19.29 pmol/l) insignificantly lower in SCH patients with positive anti-TPO antibodies (p > 0.05). Conclusions This study highlights the potential association between SCH and altered vitamin B12 status, particularly evident in HoloTC levels. The presence of positive anti-TPO antibodies and the degree of elevation in TSH levels may exacerbate vitamin B12 deficiency in SCH patients.
PubMed: 38957249
DOI: 10.7759/cureus.61513 -
Cureus Jun 2024Purpose The purpose of this study was to investigate the effect of dexmedetomidine (DEX) on hypotension-induced neuronal damage in a chronic cerebral hypoperfusion (CCH)...
Purpose The purpose of this study was to investigate the effect of dexmedetomidine (DEX) on hypotension-induced neuronal damage in a chronic cerebral hypoperfusion (CCH) model of rats, an established model of cerebral white matter lesions (WML) in humans, which is prevalent in the elderly and closely related to cognitive decline. Methods The CCH model rats were randomly assigned to one of four groups: normotension + no DEX (NN) group (n = 6), normotension + DEX (ND) group (n = 6), hypotension + no DEX (HN) group (n = 6), or hypotension + DEX (HD) group (n = 6). Under isoflurane anesthesia, mean arterial blood pressure was maintained at or above 80 mmHg (normotension) or below 60 mmHg (hypotension) for a duration of two hours. The DEX groups received 50 μg of DEX intraperitoneally. Two weeks later, the Y-maze test and, after preparing brain slices, immunohistochemical staining were performed using antibodies against neuronal nuclei (NeuN), microtubule-associated protein 2 (MAP2), glial fibrillary acidic protein (GFAP), and Ionized calcium-binding adapter molecule 1 (Iba1). Results Behavioral observations showed no significant differences among the groups. Significant reductions of both NeuN-positive cells and the MAP2-positive area were found in the hippocampal CA1 in the HN group compared with NN and ND groups, but not in the HD group. GFAP and Iba-1-positive areas were significantly increased in the HN group, but not in the HD group. Conclusion DEX significantly ameliorated hypotension-induced neuronal damage and both astroglial and microglial activation in the CA1 region of CCH rats.
PubMed: 38957242
DOI: 10.7759/cureus.61522 -
Cureus Jun 2024Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial, venous, or microvascular thrombosis, pregnancy morbidity, or non-thrombotic...
Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial, venous, or microvascular thrombosis, pregnancy morbidity, or non-thrombotic manifestations in patients with persistent antiphospholipid antibodies (aPL). Catastrophic APS is a rare and severe form of APS that is defined by the presence of multiple vascular occlusive events. When a patent foramen ovale (PFO) is present, paradoxical embolization can occur, simultaneously leading to arterial and venous thrombosis. We present a complex clinical case of a patient who presented with multiple arterial and venous thrombotic events with positive aPL. The suspicion of catastrophic APS was removed when a PFO was found in a transesophageal echocardiogram, justifying paradoxical embolization. This emphasizes the importance of searching for PFO in patients with APS presenting with simultaneous venous and arterial thrombosis for management and prognosis purposes.
PubMed: 38957237
DOI: 10.7759/cureus.61539 -
Cureus Nov 2023Pemphigus erythematosus is an uncommon autoimmune bullous skin disorder with clinical, histological, and serological characteristics that overlap with lupus...
Pemphigus erythematosus is an uncommon autoimmune bullous skin disorder with clinical, histological, and serological characteristics that overlap with lupus erythematosus and pemphigus foliaceus. The autoantigens are desmoglein 3, desmoglein 1, and desmosomal adhesion proteins in keratinocytes. When these bonds are disrupted, it causes acantholysis of keratinocytes, leading to the fluid collection between layers. Hence, the patient will present clinically with small flaccid bullae with crusting and scaling, mainly on the seborrheic areas. We report the case of a 21-year-old female presenting to us with multiple hyperkeratotic plaques, mainly on the seborrheic areas, including the face, chest, and elbows. The patient was evaluated further, and based on clinical and laboratory investigations, the diagnosis of pemphigus erythematosus associated with anti-double-stranded deoxyribonucleic acid (anti-dSDNA) and anti-nuclear antibody (ANA) positivity was made. The patient was then managed using immunosuppressant therapy, and the entire course has been detailed in this case report.
PubMed: 38957191
DOI: 10.7759/cureus.49268 -
Journal of Agricultural and Food... Jul 2024Nanobodies (Nbs) serve as powerful tools in immunoassays. However, their small size and monovalent properties pose challenges for practical application. Multimerization...
Nanobodies (Nbs) serve as powerful tools in immunoassays. However, their small size and monovalent properties pose challenges for practical application. Multimerization emerges as a significant strategy to address these limitations, enhancing the utilization of nanobodies in immunoassays. Herein, we report the construction of a -specific fenobody (Fb) through the fusion of a nanobody to ferritin, resulting in a self-assembled 24-valent nanocage-like structure. The fenobody exhibits a 35-fold increase in avidity compared to the conventional nanobody while retaining good thermostability and specificity. Leveraging this advancement, three ELISA modes were designed using Fb as the capture antibody, along with unmodified Nb422 (FbNb-ELISA), biotinylated Nb422 (FbBio-ELISA), and phage-displayed Nb422 (FbP-ELISA) as the detection antibody, respectively. Notably, the FbNb-ELISA demonstrates a detection limit (LOD) of 3.56 × 10 CFU/mL, which is 16-fold lower than that of FbBio-ELISA and similar to FbP-ELISA. Moreover, a fenobody and nanobody sandwich chemiluminescent enzyme immunoassay (FbNb-CLISA) was developed by replacing the TMB chromogenic substrate with luminal, resulting in a 12-fold reduction in the LOD. Overall, the ferritin-displayed technology represents a promising methodology for enhancing the detection performance of nanobody-based sandwich ELISAs, thereby expanding the applicability of Nbs in food detection and other fields requiring multivalent modification.
Topics: Ferritins; Single-Domain Antibodies; Salmonella; Enzyme-Linked Immunosorbent Assay; Limit of Detection; Antibody Affinity; Antibodies, Bacterial; Immunoassay
PubMed: 38957086
DOI: 10.1021/acs.jafc.4c03606