Tae Sun Ha

The role of corticosteroid in hemorrhagic bullous Henoch Schönlein purpura.

References 1. Bakkeheim E, Mowinckel P, Carlsen KH, Håland G, Carlsen KC. Paracetamol in early infancy: the risk of childhood allergy and asthma. Acta Paediatr 2011; 100: 90–6. 2. Persky V, Piorkowski J, Hernandez E, Chavez N, Wagner-Cassanova C, Vergara C, et al. Prenatal exposure to acetaminophen and respiratory symptoms in the first year of life. Ann Allergy Asthma Immunol 2008; 101: 271–8. 3. Shaheen S, Potts J, Gnatiuc L, Makowska J, Kowalski ML, Joos G, et al. The relation between paracetamol use and asthma: a GA2LEN European case-control study. Eur Respir J 2008; 32: 1231–6.

Association of Parvovirus B19 Infection with Systemic Lupus Erythematosus: Role of Th1 Predominance

To the Editor: We read with interest the article by Hession, et al 1 that described a 59-year-old woman who developed systemic lupus erythematosus (SLE) after parvovirus B19 infection; they wondered whether this phenomenon might be due to clinical mimicry or autoimmune induction1. Although not extensively studied to date, some reports show Th1-type cytokines might be increased during parvovirus B19 infection2. Isa, … Address correspondence to Dr. J.I. Shin, Department of Pediatrics, Yonsei University College of Medicine, Sungsan-Ro 250, Seodaemun-Ku, 120-752, CPO Box 8044, Seoul, Korea. E-mail: shinji{at}yuhs.ac

Is there a link between Escherichia coli septicemia and the onset of systemic lupus erythematosus? Comment on: overlapping juvenile idiopathic arthritis and systemic lupus erythematosus: a case report (Rheumatol Int. 2011 May; 31(5):695-698).

We read with great interest the contribution by Bazso et al. [1]. They reported the case of a 12-year-old girl with juvenile idiopathic arthritis (JIA) who developed systemic lupus erythematosus (SLE) after 10 years and speculated a few hypotheses of “shared autoimmunity,” the complete dysregulation of the immune system, and the side eVect of the anti-TNF therapy. However, we would like to suggest a diVerent and possible pathomechanism of the overlapping JIA and SLE case. The patient presented Escherichia coli (E. coli) septicemia at the age of 22 and subsequently developed clinical, immunological, and pathological manifestations fulWlling the diagnostic criteria of SLE within the following 8 weeks. SigniWcantly, Uthman et al. [2] also reported a case of SLE following E. coli sepsis in a 72-year-old woman, postulating three plausible pathomechanisms. Firstly, Robertson and Pisetsky [3] reported that Wve of the eight patients with E. coli bacteremia demonstrated increased levels of antibodies to single-stranded (ss) DNA from E. coli. Secondly, Gilkeson et al. [4] showed that normal mice immunized with ssDNA derived from E. coli developed an immune-mediated proliferative glomerulonephritis secondary to renal deposition of anti-DNA antibodies as in SLE. Thirdly, E. coli is known to produce heat shock protein (HSP), and Schultz et al. [5] suggested a role of HSP in the pathogenesis of rheumatic diseases like SLE. The host initially reacts to microbial infections with an enhanced cellular and humoral response to the microbial HSP, and cross-reactivity may occur with the HSP of the stressed host because of structural similarities to the microbial HSP [5]. Therefore, there is a possibility that E. coli septicemia might play a critical role as an inducer in the development of SLE in the Bazso et al.’s patient. However, further studies are necessary to elucidate the exact relationship and molecular pathogenic pathway between the JIA and SLE overlap in the future.

Effect of rituximab in MCNS: a role for IL-13 suppression?

We read with great interest the article by Aditi Sinha and Arvind Bagga (Rituximab therapy in nephrotic syndrome: implications for patients’ management. Nat. Rev. Nephrol. 9, 154–169; 2013).1 These authors reported the beneficial effects of rituxi mab treatment in patients with nephrotic syndrome and speculated that rituximab might cause apoptosis via complementdependent cytotoxicity and antibody-dependent cytotoxicity, leading to rapid depletion of B cells.1 Furthermore, rituximab is reported to induce T-regulatory and B-regulatory cell populations, restore immune tolerance, and attenuate the downregulation of sphingomyelinaselike phosphodiesterase 3b in podocytes.1 We would like to add another possible mechanism that may explain the beneficial effect of rituximab on minimal-change nephrotic syndrome (MCNS). Although rare, some reports have shown that Th2 cytokines, such as interleukin (IL)-13, may play an important role in the pathogenesis of MCNS.2–4 Yap et al. reported that CD4+ and CD8+ IL-13 mRNA expression was increased in patients with nephrotic relapse compared with those in remission, healthy individuals, and patient controls (children with viral infections, but without idiopathic nephrotic syndrome; P <0.008) and that this finding was related to an increase in expression of cytoplasmic IL-13 in phorbol myristate acetate/ionomycin-activated CD3+ cells (6.66 ± 3.39%) in patients with nephrotic relapse compared with expression in patients in the remission phase (2.59 ± 1.35%, P <0.0001).2 Yap et al. speculated that IL-13 may act on monocytes to produce vascular permeability factors Effect of rituximab in MCNS: a role for IL‐13 suppression?

Hypophosphatemia in patients with autosomal dominant polycystic kidney disease: the role of fibroblast growth factor 23 or loss of sodium/phosphate cotransporter?

1. Przedlacki J. Comments on KDIGO clinical practice guidelines for biphosphonate treatment of chronic kidney disease. Kidney Int 2010; 78: 1186. 2. Kidney Disease-Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int Suppl 2009; 76: S1–S130. 3. Marron B, Remon C, Perez-Fontan M et al. Benefits of preserving residual renal function in PD. Kidney Int 2008; 73: S42–S51. 4. Health Science Authority, Singapore Adverse Drug Reaction News. August 2010, vol 12, No. 2, p 2. 5. FDA Drug Safety Newsletter, vol 2, No. 2, 2009. Zoledronic acid (marketed as Reclast): Renal impairment and acute renal failure. http://www.fda.gov/Drugs/DrugSafety/DrugSafetyNewsletter/ ucm167883.htm. 6. MHRA Drug Safety Update: vol 3. Issue 9, April 2010. Intravenous zoledronic acid: adverse effects on renal function. http://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/ CON076501. 7. HSA website Dear Healthcare Professional Letters (DHCPL). http://www.hsa.gov.sg/DHCPL.

The role of interleukin-23/interleukin-17 axis in the development of systemic lupus erythematosus among patients with tuberculosis: comment on: Lin YC, Liang SJ, Liu YH et al.: tuberculosis as a risk factor for systemic lupus erythematosus: results of a nationwide study in Taiwan. (Rheumatol Int. 2011 Mar 18. [Epub ahead of print]).

Dear Editor, We read with great interest the contribution by Lin et al. [1]. They evaluated the relationship between Mycobacterium tuberculosis (TB) and systemic lupus erythematosus (SLE) and reported an increased risk of precipitating SLE among patients with TB (P \ 0.0001). However, they did not explicate the exact mechanism. We would like to suggest a possible pathomechanism of SLE in patients with TB. During primary TB, interferon (IFN)-c, produced by CD4(?) T helper (Th) 1 cells, and interleukin (IL)-17, largely produced by Th17 cells and suppressed by IFN-c, are induced [2]. Both IFN-c and IL-17 promote cell recruitment and granuloma organization throughout infection [2]. However, dysregulated balance of Th1 and Th17 cells, as a shift of the response toward excessive IL-17, sustains extensive neutrophil recruitment and tissue damage during the chronic phase of primary TB [2, 3]. Both the IL-17 and the Th17 response to TB are dependent upon IL-23. According to a study by Shah et al. [4], patients with SLE had an increased CD4(?) IL-17 cells compared with healthy subjects, indicating an altered balance of Th1 and Th17 cell responses in SLE and suggesting a role of IL-17 in the pathogenesis of lupus. Enhanced Th17 cell response correlated with disease activity in patients with SLE. Doreau et al. [5] also found that IL-23-dependent IL-17 controlled the survival and proliferation of human B cells and their differentiation into immunoglobulin-secreting cells through the nuclear factor-kappa B-regulated transcription factor Twist-1 in SLE. Ex vivo inductions of IL17 by IL-23 were significantly higher in SLE patients than controls (all P \ 0.05) [6]. Recently and importantly, Kyttaris et al. [7] demonstrated that IL-23R-deficient lupus-prone C57BL/6-lpr/lpr mice display decreased numbers of CD3(?)CD4(-) CD8(-) cells and IL-17A-producing cells in the lymph nodes and produce less anti-DNA antibodies. These data all show that the activated IL-23/IL-17 axis is important for the autoinflammatory immunity in SLE. Therefore, there is a possibility that IL-23-mediated signaling and IL-17 might play a critical role in the development of SLE among patients with TB, and it would be interesting to measure the levels of IL-23 and IL-17 in those patients. However, further studies are necessary to elucidate the precise molecular role and signaling transduction pathway of IL-23 and IL-17 including IFN-c during the process of TB and SLE overlap. IL-23or IL-17blocking as a new therapeutic target in TB and SLE should also be further studied in the future.

Dense deposit disease in Korean children: a multicenter clinicopathologic study.

The purpose of this study was to investigate the clinical, laboratory, and pathologic characteristics of dense deposit disease (DDD) in Korean children and to determine whether these characteristics differ between Korean and American children with DDD. In 2010, we sent a structured protocol about DDD to pediatric nephrologists throughout Korea. The data collected were compared with previously published data on 14 American children with DDD. Korean children had lower 24-hr urine protein excretion and higher serum albumin levels than American children. The light microscopic findings revealed that a higher percentage of Korean children had membranoproliferative glomerulonephritis patterns (Korean, 77.8%; American, 28.6%, P = 0.036), whereas a higher percentage of American children had crescents (Korean, 0%; American, 78.6%, P < 0.001). The findings from the electron microscopy revealed that Korean children were more likely to have segmental electron dense deposits in the lamina densa of the glomerular basement membrane (Korean, 100%; American, 28.6%, P = 0.002); mesangial deposit was more frequent in American children (Korean, 66.7%; American, 100%, P = 0.047). The histological findings revealed that Korean children with DDD were more likely to show membranoproliferative glomerulonephritis patterns than American children. The degree of proteinuria and hypoalbuminemia was milder in Korean children than American children.

The significance of T helper 1 cell-derived cytokines in patients with systemic lupus erythematosus with acquired thrombotic thrombocytopenic purpura.

To the Editor We read with great interest the contribution by Muscal et al.1 They reported the development of systemic autoimmunity such as systemic lupus erythematosus (SLE) and antiphospholipid antibodies in children with acquired thrombotic thrombocytopenic purpura (TTP). We would like to suggest some potential pathologic mechanisms on the development of concurrent SLE in relation to TTP. Kakishita2 found that TTP after bone marrow transplantation (BMT) could be predicted at an …

Hypophosphatemia in patients with autosomal dominant polycystic kidney disease: the role of fibroblast growth factor 23 or loss of sodium|[sol]|phosphate cotransporter|[quest]|

1. Przedlacki J. Comments on KDIGO clinical practice guidelines for biphosphonate treatment of chronic kidney disease. Kidney Int 2010; 78: 1186. 2. Kidney Disease-Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int Suppl 2009; 76: S1–S130. 3. Marron B, Remon C, Perez-Fontan M et al. Benefits of preserving residual renal function in PD. Kidney Int 2008; 73: S42–S51. 4. Health Science Authority, Singapore Adverse Drug Reaction News. August 2010, vol 12, No. 2, p 2. 5. FDA Drug Safety Newsletter, vol 2, No. 2, 2009. Zoledronic acid (marketed as Reclast): Renal impairment and acute renal failure. http://www.fda.gov/Drugs/DrugSafety/DrugSafetyNewsletter/ ucm167883.htm. 6. MHRA Drug Safety Update: vol 3. Issue 9, April 2010. Intravenous zoledronic acid: adverse effects on renal function. http://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/ CON076501. 7. HSA website Dear Healthcare Professional Letters (DHCPL). http://www.hsa.gov.sg/DHCPL.

The role of interferon-gamma and interleukin 17 between Helicobacter pylori infection and Graves' disease: Comment on: Identification of a correlation between Helicobacter pylori infection and Graves' disease. Helicobacter 2010;15(6):558-62.

Dear Editor, We read with great interest the contribution by Bassi et al. [1]. They reported the increased prevalence of Helicobacter pylori in Graves’ patients and the association between H. pylori and Graves’ disease, but did not mention the exact pathomechanism. We would like to suggest a possible mechanism in the pathogenesis of Graves’ disease by H. pylori infection. Although not extensively studied yet, there have been some reports showing the expression of proinflammatory and T helper type 1 (Th1) cytokines, such as interferon (IFN)-gamma and interleukin (IL)-17, was increased in the H. pylori-induced inflammatory response [2,3]. Especially, H. pylori stimulated dendritic cells at mucosal sites, leading to increased IFN-gamma and IL-17 expression from CD4 (+) T lymphocytes [3]. Interestingly, Nagayama et al. [4] found that only 7% of IFN-gamma knockout (KO) mice became hyperthyroid, while wild-type BALB ⁄ c mice in which 60% developed hyperthyroidism, suggesting an important role of IFN-gamma in the development of Graves’ disease. It was also demonstrated by Nanba et al. [5] that the proportion of peripheral Th1 cells and Th17 cells was higher in patients with intractable Graves’ disease than in control subjects (p < .05), but that of peripheral Th2 cells was lower (p < .001). These results implicates that Th1 cytokines predominance by H. pylori would favor the occurrence of Graves’ disease, but not Th2 cytokines. Quite recently, Kabir [6] revealed that IL-17 induces IL-8 secretion by activating the ERK 1 ⁄ 2 MAP kinase pathway and the released IL-8 attracts neutrophils promoting inflammation in human immune system. In addition, Doreau et al. [7] found that IL-17 concentrations were higher in the serum of patients with systemic lupus erythematosus than in that of healthy people, which means that IL-17 abundance correlated with the disease severity in autoimmune diseases. Therefore, it is possible that IFN-gamma and IL-17 induced by Th1 and Th17 cells, respectively, as well as H. pylori virulence factors may be involved in the pathogenesis and development of Graves’ disease by H. pylori infection. However, further studies are necessary to elucidate which factors of H. pylori infection might be included and the precise molecular role of IFN-gamma and IL-17 in the regulatory and signaling pathway of the disease in the future.