Simon H Jiang

• B. Med, MMed (Hons), FRACP, PhD
• Fellow at Australian National University

Objective: Phenotypic diversity of autoimmune diseases presents an ongoing diagnostic and drug development challenge for clinicians and scientists. Recent discovery of mutations in RELA (encoding RELA) in patients with different diagnoses has highlighted that different pathogenic molecular mechanism are at play and may explain the observed phenotyp...

Whole-exome sequencing of two unrelated kindreds with systemic autoimmune disease featuring antinuclear antibodies with IgG4 elevation uncovered an identical ultrarare heterozygous TNIP1Q333P variant segregating with disease. Mice with the orthologous Q346P variant developed antinuclear autoantibodies, salivary gland inflammation, elevated IgG2c, s...

The heterogeneous composition of cellular transcriptomes poses a major challenge for detecting weakly expressed RNA classes, as they can be obscured by abundant RNAs. Although biochemical protocols can enrich or deplete specified RNAs, they are time-consuming, expensive and can compromise RNA integrity. Here we introduce RISER, a biochemical-free t...

DNA methylation plays essential roles in regulating physiological processes, from tissue and organ development to gene expression and aging processes and has emerged as a widely used biomarker for the identification of body fluids and age prediction. Currently, methylation markers are targeted independently at specific CpG sites as part of a multip...

DNA methylation plays essential roles in regulating physiological processes, from tissue and organ development to gene expression and aging processes and has emerged as a widely used biomarker for the identification of body fluids and age prediction. Currently, methylation markers are targeted independently at specific CpG sites, as part of a multi...

Autosomal dominant loss-of-function (LoF) variants in cytotoxic T-lymphocyte associated protein 4 ( CTLA4 ) cause immune dysregulation with autoimmunity, immunodeficiency and lymphoproliferation (IDAIL). Incomplete penetrance and variable expressivity are characteristic of IDAIL caused by CTLA-4 haploinsufficiency (CTLA-4h), pointing to a role for...

Background To determine the safety and efficacy of biological agents used in the treatment of systemic lupus erythematosus (SLE) in adults. Methods Systematic review and meta-analysis following PRISMA guidelines. Data sources MEDLINE (through Pubmed), EMBASE, Cochrane library, Clinicaltrials.gov, Australianclinicaltrials.gov.au, ANZCTR.org.au and...

Background: To determine the safety and efficacy of biological agents used in the treatment of systemic lupus erythematosus (SLE) in adults. Methods: Systematic review and meta-analysis following PRISMA guidelines Data sources: MEDLINE (through Pubmed), EMBASE, Cochrane library, Clinicaltrials.gov, Australianclinicaltrials.gov.au, ANZCTR.org.au and...

Background Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease characterized by development of autoantibodies and multiorgan involvement. Kidney involvement, termed lupus nephritis, has major impact on life expectancy. It is increasingly recognized that SLE is likely a common clinical manifestation of pathophysiologically di...

Diffuse large B-cell lymphoma (DLBCL) is the most common form of B-cell non-Hodgkin lymphoma (B-NHL) with significant morbidity and mortality despite advancements in treatment. Lymphoma and autoimmune disease both result from breakdowns in normal cell regulatory pathways, and epidemiological studies have confirmed both that B-NHL is more likely to...

Accumulation of immunoglobulin and complement components within the kidneys is a hallmark of glomerulonephritis. Staining and detection of IgG, IgA, IgM, and C3 deposits can assist in diagnosing the underlying causes of nephritis and has implications for the pathological processes underpinning glomerulonephritis. Here, we describe a protocol to det...

Background and Objectives Chronic kidney disease progression to ESKD is associated with a marked increase in mortality and morbidity. Its progression is highly variable and difficult to predict. Methods This is an observational, retrospective, single-centre study. The cohort was patients attending hospital and nephrology clinic at The Canberra Hos...

B cell self-tolerance is maintained through multiple checkpoints, including restraints on intracellular signaling and cell trafficking. P2RY8 is a receptor with established roles in germinal center (GC) B cell migration inhibition and growth regulation. Somatic P2RY8 variants are common in GC-derived B cell lymphomas. Here, we identify germline nov...

We identify an intronic deletion in VANGL1 that predisposes to renal injury in high risk populations through a kidney-intrinsic process. Half of all SLE patients develop nephritis, yet the predisposing mechanisms to kidney damage remain poorly understood. There is limited evidence of genetic contribution to specific organ involvement in SLE.¹ • Ch...

Objective To compare the frequency of rare variants in genes of the pathophysiologically relevant endosomal Toll-like receptor (eTLR) pathway and any quantifiable differences in variant rarity, predicted deleteriousness, or molecular proximity in patients with systemic lupus erythematosus (SLE) and healthy controls. Patients and methods 65 genes a...

Expanded carrier screening (ECS) for recessive monogenic diseases requires prior knowledge of genomic variation, including DNA variants that cause disease. The composition of pathogenic variants differs greatly among human populations, but historically, research about monogenic diseases has focused mainly on people with European ancestry. By compar...

Background: C3 glomerulonephritis is a recently described entity with heterogeneous histopathological features. This study was conducted to assess the effect of reclassification of C3 glomerulopathies on renal outcomes, mortality, and response to therapy. Methods: We undertook a retrospective analysis of 857 renal biopsies collected at The Canbe...

Autoimmune disease is a substantial cause of morbidity and is strongly influenced by genetic risk. Extensive efforts have characterised the overall genetic basis of many autoimmune diseases, typically by investigation of common variants. Whilst these common variants have modest effects and may cumulatively predispose to disease, it is also increasi...

Genetic primary immunodeficiency diseases are increasingly recognized, with pathogenic mutations changing the composition of circulating leukocyte subsets measured by flow cytometry (FCM). Discerning changes in multiple subpopulations is challenging, and subtle trends might be missed if traditional reference ranges derived from a control population...

Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease. It is thought that many common variant gene loci of weak effect act additively to predispose to common autoimmune diseases, while the contribution of rare variants remains unclear. Here we describe that rare coding variants in lupus-risk genes are present in most SLE...

Acute kidney injury (AKI) can be fatal and is a well-defined risk factor for the development of chronic kidney disease. Group 2 innate lymphoid cells (ILC2s) are innate producers of type-2 cytokines and are critical regulators of homeostasis in peripheral organs. However, our knowledge of their function in the kidney is relatively limited. Recent e...

Background Recurrence of primary glomerulonephritis in the post-transplant period has been described in the literature but the risk remains poorly quantified and its impact on allograft outcomes and implications for subsequent transplants remain under-examined. Here we describe the rates and timing of post-transplant glomerulonephritis recurrence f...

Introduction: Maintaining fluid intake sufficient to reduce arginine vasopressin (AVP) secretion has been hypothesised to slow kidney cyst growth in autosomal dominant polycystic kidney disease (ADPKD). However, evidence to support this as a clinical practice recommendation is of poor quality. The aim of the present study is to determine the long-...

Background: Adequate haemodialysis (HD) in people with end-stage kidney disease (ESKD) is reliant upon establishment of vascular access, which may consist of arteriovenous fistula, arteriovenous graft, or central venous catheters (CVC). Although discouraged due to high rates of infectious and thrombotic complications as well as technical issues th...

Background: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by multiple organ involvement. Lupus nephritis (LN) is a common manifestation with a wide variety of histological appearances. Matrix metalloproteinases (MMP) 2 and 9 are gelatinases capable of degrading glomerular basement membrane type IV collagen, which...

Background and aims Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Twin studies indicate a strong genetic contribution to lupus, yet often the pathogenic variant remains unknown. A better understanding of the individual genetic causes of SLE will enable personalised therapies. Using next generation sequencing technologies...

Background Kidney transplantation confers superior outcomes for patients with end stage kidney disease, and live donor kidneys associate with superior outcomes compared to deceased donor kidneys. Modern immunosuppression has improved rejection rates and transplant survival and, as a result, recurrence of glomerulonephritis has emerged as a major ca...

Yamamoto et al. have studied T follicular helper (TFH) and germinal centre (GC) responses after infection of rhesus macaques (RM) infected with simian immunodeficiency virus (SIV). In this study the authors examined the behaviour of TFH, reproducing infection-associated TFH accumulation and their association with the quality of antibody responses a...

T follicular helper (Tfh) cells are crucial to induce protective extrafollicular and germinal center antibody responses against protein antigens. Over the last decade, control of Tfh cell numbers has emerged as an important regulatory checkpoint which, when perturbed, may lead to production of autoantibodies. Recent progress in understanding how Tf...

Objective Systemic lupus erythematosus (SLE) is a chronic and heterogeneous autoimmune disease. Both twin and sibling studies indicate a strong genetic contribution to lupus, but in the majority of cases the pathogenic variant remains to be identified. The genetic contribution to disease is likely to be greatest in cases with early onset and severe...

A significant proportion of peritoneal dialysis (PD) patients will have abrupt technique failure requiring conversion to haemodialysis, often using temporary vascular catheters as bridging access. However, vascular catheter use has been associated with increased mortality and great effort has been made to reduce their use. Just under two decades ag...

Purpose: Peritonitis can be a severe complication of peritoneal dialysis (PD) due to associated morbidity and mortality. Non-tuberculous mycobacteria (NTM) are a rare cause of PD peritonitis, with high rates of catheter removal and conversion to haemodialysis, and a reported mortality as high as 40 %. The incidence, culprit NTM species, and outcom...

Antibody-mediated rejection (AMR) is a recognized cause of allograft loss in kidney transplant recipients. A range of therapies targeting removal of circulating donor-specific antibodies (DSAs), blocking their effect or reducing production have been reported. We conducted a systematic review to determine the efficacy of treatments for acute AMR in...

Establishing and maintaining hemodialysis access are major challenges in dialysis patient care. The impact of implementing guideline recommendations around vascular access surveillance, which lacks strong evidence, is poorly understood. We report the results of a vascular access surveillance and early intervention program upon hemodialysis thrombos...

Peritoneal dialysis-associated peritonitis (PD-peritonitis) due to Mycobacterium spp is uncommon. Non-tuberculous Mycobacterium (NTB) PD-peritonitis can present in a similar fashion to more common causes of bacterial PD-peritonitis. We describe the first reported case of multiresistant Mycobacterium fortuitum PD-peritonitis in an Australian patient...

It has been recommended that patients should be admitted for 24 h of observation after percutaneous renal biopsy. This may be performed in the ambulatory outpatient setting, though its safety in this setting is an area of debate. We aim to demonstrate the safety of biopsy in the ambulatory outpatient setting. We performed a retrospective cohort stu...

The stent placement in patients with atherosclerotic renal artery stenosis and impaired renal function (STAR) and revascularization versus medical therapy for renal-artery stenosis (ASTRAL) trials concluded that renal artery angioplasty was not superior to medical management in delaying progression to renal failure or controlling blood pressure in...

Kidney International aims to inform the renal researcher and practicing nephrologists on all aspects of renal research. Clinical and basic renal research, commentaries, The Renal Consult, Nephrology sans Frontieres, minireviews, reviews, Nephrology Images, Journal Club. Published weekly online and twice a month in print.

Monitoring of blood flows in arteriovenous fistulae and arteriovenous grafts is recommended to predict access thrombosis. The ultrasound dilution technique (UDT) is the gold standard. We compare a recently described haemoglobin dilution technique (HDT) with the UDT in measurement of vascular access flow. Access blood flow was measured in 67 stable...

A 27-year-old man presented with a 10-day history of dysuria, oliguria, and left-sided flank pain. On the day of presentation he developed hiccups. He had poorly controlled type 1 diabetes mellitus and was an active recreational intravenous drug user. He was febrile to 38.71. Physical examination demonstrated only mild left-sided flank pain. Urine...

To investigate the effectiveness of hot water immersion for the treatment of Physalia sp. (bluebottle or Portuguese Man-of-War) stings. Open-label, randomised comparison trial. Primary analysis was by intention to treat, with secondary analysis of nematocyst-confirmed stings. One halfway interim analysis was planned. Surf lifesaving first aid facil...