Corrigendum to "Massive Acetaminophen Overdose Treated Successfully with N-Acetylcysteine, Fomepizole, and Hemodialysis".

[This corrects the article DOI: 10.1155/2021/6695967.].

Massive Acetaminophen Overdose Treated Successfully with N-Acetylcysteine, Fomepizole, and Hemodialysis.

Acetaminophen overdose is one of the most common causes of acute hepatic failure in the developed world. There is strong evidence for N-acetylcysteine (NAC) as a safe and effective antidote for acetaminophen toxicity. However, there is less clarity in the management of massive overdoses (acute, single ingestions > 500 mg/kg with 4-hour equivalent concentrations ~6000 µmol/L) which are often associated with metabolic acidosis and multiorgan dysfunction. In such ingestions, the role of adjuvant treatments such as fomepizole and extracorporeal removal is unclear. We present a case of a 20-year-old female presenting with an acute ingestion of over 120 grams (1764.7 mg/kg) and an acetaminophen concentration of 5880 µmol/L who developed refractory shock, decreased level of consciousness, and metabolic acidosis requiring mechanical ventilation and vasopressor support. She was treated with gastric decontamination with activated charcoal, IV NAC, fomepizole, and hemodialysis. The patient had complete clearance of acetaminophen by 32 hours after presentation and normalization of her acid base and hemodynamic status without any organ failure. This case highlights the potential benefit of a triple strategy of NAC, fomepizole, and early hemodialysis in massive acetaminophen overdose, potentially sparing complications of prolonged intubation and ICU hospitalization.

Immunoglobulin-A Vasculitis With Renal Involvement in a Patient With COVID-19: A Case Report and Review of Acute Kidney Injury Related to SARS-CoV-2.

RATIONALE: Acute kidney injury is a common complication of COVID-19 and is associated with significantly increased mortality. The most frequent renal biopsy finding with SARS-CoV-2 infection is acute tubular injury; however, new onset glomerular diseases have been reported. The development of persistent urinary abnormalities in patients with COVID-19 should prompt consideration for renal biopsy to rule out glomerulonephritis. PRESENTING CONCERNS: A 30-year-old man with no prior medical history presented to the emergency department with symptoms of COVID-19 and new onset painful purpuric rash, arthralgia, and abdominal pain. SARS-CoV-2 infection was confirmed with nucleic acid testing and laboratory investigations revealed preserved renal function with dysmorphic hematuria and nephrotic range proteinuria. DIAGNOSIS: A skin biopsy of the purpuric rash was performed, which demonstrated leukocytoclastic vasculitis. Renal biopsy revealed focally crescentic and segmentally necrotizing IgA nephropathy. Overall, given the clinical syndrome of glomerulonephritis with purpuric rash, arthralgia, and abdominal pain, the presentation is most in keeping with a diagnosis of IgA vasculitis in the setting of COVID-19. INTERVENTIONS: The patient was treated conservatively for COVID-19 in the community. A 7-day course of prednisone was started for the vasculitic rash. IgA nephropathy was managed conservatively with blood pressure control and RAAS blockade with losartan. OUTCOMES: With conservative management, the patient's COVID-19 symptoms resolved completely and he did not require hospital admission. Following prednisone therapy, the patient's rash, arthralgia, and abdominal pain improved. However, despite resolution of COVID-19, hematuria and proteinuria persisted. With the initiation of RAAS blockade, renal function remained stable and proteinuria improved dramatically at 6 weeks. NOVEL FINDINGS: De novo glomerulonephritis is a renal manifestation of SARS-CoV-2 infection beyond acute tubular injury. IgA vasculitis appears to be a rare complication of COVID-19.

Expanding the Role of Complement Therapies: The Case for Lupus Nephritis.

The complement system is an innate immune surveillance network that provides defense against microorganisms and clearance of immune complexes and cellular debris and bridges innate and adaptive immunity. In the context of autoimmune disease, activation and dysregulation of complement can lead to uncontrolled inflammation and organ damage, especially to the kidney. Systemic lupus erythematosus (SLE) is characterized by loss of tolerance, autoantibody production, and immune complex deposition in tissues including the kidney, with inflammatory consequences. Effective clearance of immune complexes and cellular waste by early complement components protects against the development of lupus nephritis, while uncontrolled activation of complement, especially the alternative pathway, promotes kidney damage in SLE. Therefore, complement plays a dual role in the pathogenesis of lupus nephritis. Improved understanding of the contribution of the various complement pathways to the development of kidney disease in SLE has created an opportunity to target the complement system with novel therapies to improve outcomes in lupus nephritis. In this review, we explore the interactions between complement and the kidney in SLE and their implications for the treatment of lupus nephritis.

Cis association of leukocyte Ig-like receptor 1 with MHC class I modulates accessibility to antibodies and HCMV UL18.

Leukocyte Ig-like receptor (LIR) 1 (CD85j/ILT2/LILRB1) is an inhibitory receptor with broad specificity for MHC class I (MHC-I) and the human CMV MHC-I homologue UL18. LIR-1 can inhibit NK cells through the conventional interaction with MHC-I expressed on a target cell (in trans) but the nature and the effects of LIR-1 interactions with MHC-I in cis are not well understood. Here we show that MHC-I expressed in cis has an impact on the detection of LIR-1 with various antibodies. We found the cis interaction alters recognition by only one of two antibodies known to block functional trans recognition by LIR-1 on NK cells. Specifically, we observed an enhancement of recognition with GHI/75 in the presence of various MHC-I alleles on 721.221 cells. We found that blocking the LIR-1 contact site with anti-MHC-I antibodies decreased detection of LIR-1 with GHI/75. We also observed a decrease in GHI/75 following acid denaturation of MHC-I. Finally, disruption of LIR-1 cis interactions with MHC-I significantly enhanced UL18-Fc binding to NK92 cells and enhanced the relative inhibition of NK92 cells by HLA-G. These results have implications for LIR-1 function in scenarios such as infection when MHC-I levels on effector cells may be increased by IFNs.

Modulation of the inhibitory receptor leukocyte Ig-like receptor 1 on human natural killer cells.

Leukocyte Ig-like receptor 1 (LIR-1) is an inhibitory Ig superfamily receptor with broad specificity for MHC-I expressed on leukocytes including natural killer (NK) and T cells. The extent of LIR-1 expression on NK cells is quite disparate between donors but the regulation of LIR-1 in NK cells is poorly understood. We examined expression profiles of LIR-1 on NK and T lymphocytes in 11 healthy donors over 1 year. Four of the 11 donors demonstrated substantial increases in LIR-1⁺ NK cells. High levels of LIR-1 expression were not correlated with exposure to human cytomegalovirus or the fraction of CD57⁺ NK cells in the donor. LIR-1 levels on ex vivo NK and CD56⁺ T cells were increased in vitro by short term exposure to IL-2 or IL-15 compared to control but not with various other cytokines tested. Sorted CD56(bright) NK cells also increased LIR-1 expression when cultured in IL-2. Maintenance of LIR-1 on longer term NK cells was also dependent on continuous stimulation by IL-15 or IL-2. While we could not detect increases in total LIR-1 mRNA in response to cytokine treatment by qPCR, we observed a shift in activity of LIR-1 promoter reporter constructs in the presence of IL-2 favoring the more translationally active transcript from the proximal promoter. Together these results show LIR-1 on NK cells is under the control of cytokines known to drive NK cell maturation and activation and suggest availability of such cytokines may alter the NK repertoire in vivo as we observed in several donors with fluctuating levels of LIR-1 on their NK cells.

LILRB1 polymorphism and surface phenotypes of natural killer cells.

Leukocyte Ig-like receptor (LIR)-1 is an inhibitory receptor that binds a broad range of class I HLA molecules and is encoded by the LILRB1 gene within the leukocyte receptor complex. In contrast to uniform expression on monocytes and B cells, LIR-1 expression on natural killer (NK) cells varies considerably between individuals. To investigate how polymorphism is related to the observed patterns of expression, we analyzed the LILRB1 gene and its transcriptional activity in a group of individuals with various levels of expression on NK cells. We found that LILRB1 transcription is correlated with surface protein expression on NK cells. In a cohort of 24 donors, we found high expression on NK cells to be associated with three linked SNPs (AGG verses GAA) within the putative regulatory region. We also identified several new protein variants and observed variants with P, T, T, and I at positions 68, 95, 142, and 155, respectively, more frequently in donors with low expression on NK cells. These results suggest that there is a significant degree of diversity within the LILRB1 locus and that it influences expression patterns on NK cells. These genetic differences may underpin variation in individual immune responses involving LIR-1 on NK cells.