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IL36RN mutations define a severe autoinflammatory phenotype of generalized pustular psoriasis

Hussain S, Berki DM, Choon SE, Burden AD, Allen MH, Arostegui JI, et al.

J Allergy Clin Immunol, 2015 Apr;135(4):1067-1070.e9.
PMID: 25458002 DOI: 10.1016/j.jaci.2014.09.043
Matched MeSH terms: Autoimmunity/genetics*
Pathophysiology of chronic urticaria

Greaves MW

Int Arch Allergy Immunol, 2002 Jan;127(1):3-9.
PMID: 11893848 DOI: 10.1159/000048163

Chronic urticaria includes several different subsets with distinct pathophysiologies, and with important implications for investigation and treatment. Chronic 'idiopathic' urticaria represents a special challenge, which, until recently, was not taken up by dermatological or immunological investigators. However, it has now emerged that at least 30% of patients possess histamine-releasing autoantibodies against Fc epsilon R1, or less commonly IgE itself. These autoantibodies are causative. Recent work implicates complement activation in most cases. Functional (i.e. histamine releasing) autoantibodies are specific to chronic urticaria. However, immunoreactive (non-histamine-releasing) anti-Fc epsilon R1 autoantibodies can be found in sera of patients with physical urticarias and with autoimmune connective tissue and bullous diseases. The reason for the occurrence of this disease type in some individuals but not others is unclear. One possibility is the development, in genetically predisposed persons, of autoantibodies by molecular mimicry - perhaps against lipopolysaccharide of Helicobacter pylori, an organism frequently infecting the upper gastrointestinal tract of chronic urticaria patients.

Matched MeSH terms: Autoimmunity
Is hyaluronic acid filler still a potential risk factor for an autoimmune reaction?

Aljawhar NM, Sharquie IK

Med J Malaysia, 2020 07;75(4):363-367.
PMID: 32723995

BACKGROUND: Rejuvenation of the skin with hyaluronic acid (HA) filler is considered to be one of the most favourable procedures in the field of aesthetics. Nevertheless, some adverse effects still occur though infrequently, and are associated with its use. Previous research has suggested that HA filler may stimulate antibodies. Consequently, an investigation of the immune interactions associated with use of HA filler is an important area for investigation.
OBJECTIVES: The aim of this research is to investigate whether HA filler influences the initiation of an autoimmune reaction in healthy women who had received HA filler by screening for autoantibodies in the blood. Results will be compared with agematched apparently healthy control women who did not receive the filler.
METHODS: Serum samples were obtained from 44 females who had received HA filler and 44 females who had not as a control group. The enzyme-linked immunosorbent assay (ELISA) technique was utilised to measure serum concentrations of anti- Thyroglobulin (Tg), anti -thyroid peroxidase (TPO), rheumatoid factor (RF), anti-nuclear antibody (ANA) and anticentromeres.
RESULTS: The number of women who tested positive for the measured autoantibodies was not statistically significant (p=0.803) between those who had received HA filler (n=10/44, 25%) and the control group (n=11/44, 22.7%).
CONCLUSION: Based on our result HA filler procedures do not induce an autoimmune reaction in women who received HA filler compared to controls. And consequently, HA filler procedures are relatively safe, and these results contradict the findings of other non-controlled works.

Matched MeSH terms: Autoimmunity/drug effects*
Antibodies against malondialdehyde (MDA) in MRL/lpr/lpr mice: evidence for an autoimmune mechanism involving lipid peroxidation

Yahya MD, Pinnas JL, Meinke GC, Lung CC

J Autoimmun, 1996 Feb;9(1):3-9.
PMID: 8845052

Previous studies have shown that lipid peroxidative processes may play a role in disease pathogenesis in lupus-prone MRL/lpr mice. Studies were thus performed to determine if an immune response against malondialdehyde (MDA), a highly reactive byproduct of lipid peroxidation, was present in these mice. By using MDA-modified mouse serum albumin (MSA) as antigens in ELISA, we found that these mice produce high levels of MDA-specific antibodies in the complement-fixing IgG2a and IgG2b subclasses. Anti-MDA antibodies were also found in MRL/+ mice but in significantly lower levels. The specificity of these antibodies was verified by inhibition ELISA. MDA may contribute to disease pathogenesis in these mice by altering the immunogenicity of self molecules, eliciting an immune response and forming immune complexes that may deposit in tissues.

Matched MeSH terms: Autoimmunity*
Hyperferritinaemia: An Iron Sword of Autoimmunity

Giemza-Stokłosa J, Islam MA, Kotyla PJ

Curr Pharm Des, 2019;25(27):2909-2918.
PMID: 31686632 DOI: 10.2174/1381612825666190709202804

BACKGROUND: Ferritin is a molecule that plays many roles being the storage for iron, signalling molecule, and modulator of the immune response.
METHODS: Different electronic databases were searched in a non-systematic way to find out the literature of interest.
RESULTS: The level of ferritin rises in many inflammatory conditions including autoimmune disorders. However, in four inflammatory diseases (i.e., adult-onset Still's diseases, macrophage activation syndrome, catastrophic antiphospholipid syndrome, and sepsis), high levels of ferritin are observed suggesting it as a remarkable biomarker and pathological involvement in these diseases. Acting as an acute phase reactant, ferritin is also involved in the cytokine-associated modulator of the immune response as well as a regulator of cytokine synthesis and release which are responsible for the inflammatory storm.
CONCLUSION: This review article presents updated information on the role of ferritin in inflammatory and autoimmune diseases with an emphasis on hyperferritinaemic syndrome.

Matched MeSH terms: Autoimmunity*
The RUNX complex: reaching beyond haematopoiesis into immunity

Voon DC, Hor YT, Ito Y

Immunology, 2015 Dec;146(4):523-36.
PMID: 26399680 DOI: 10.1111/imm.12535

Among their diverse roles as transcriptional regulators during development and cell fate specification, the RUNX transcription factors are best known for the parts they play in haematopoiesis. RUNX proteins are expressed throughout all haematopoietic lineages, being necessary for the emergence of the first haematopoietic stem cells to their terminal differentiation. Although much progress has been made since their discoveries almost two decades ago, current appreciation of RUNX in haematopoiesis is largely grounded in their lineage-specifying roles. In contrast, the importance of RUNX to immunity has been mostly obscured for historic, technical and conceptual reasons. However, this paradigm is likely to shift over time, as a primary purpose of haematopoiesis is to resource the immune system. Furthermore, recent evidence suggests a role for RUNX in the innate immunity of non-haematopoietic cells. This review takes a haematopoiesis-centric approach to collate what is known of RUNX's contribution to the overall mammalian immune system and discuss their growing prominence in areas such as autoimmunity, inflammatory diseases and mucosal immunity.

Matched MeSH terms: Autoimmunity
Fulltext Gender differences in the clinical and serological features of systemic lupus erythematosus in Malaysian patients

Azizah MR, Ainol SS, Kong NCT, Normaznah Y, Rahim MN

Med J Malaysia, 2001 Sep;56(3):302-7.
PMID: 11732074

An analysis of the clinical and serological features of 12 male and 122 female patients with SLE was done to determine whether sex related differences exist. We found a lower incidence of mucocutaneous symptoms and arthritis but an increased incidence of discoid lesions, pleuritis and pericarditis in males at disease onset. During the disease course, there was a lower incidence of arthritis, a similar prevalence of mucocutaneous symptoms but an increased incidence of pleuritis in males with a trend towards renal involvement. These findings were however not statistically significant except for the higher incidence of thrombosis among males. Serologically, both groups showed similar frequencies of autoantibodies and hypocomplementaemia. Although the study was small, it was shown that several sex-related differences in the clinical and serological features exist in Malaysian SLE patients.
Study site: SLE Clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia

Matched MeSH terms: Autoimmunity
Fulltext Technical Considerations in Ex Vivo Human Regulatory T Cell Migration and Suppression Assays

Irekeola AA, E A R ENS, Lazim NM, Mohamud R, Yean CY, Shueb RH

Cells, 2020 02 20;9(2).
PMID: 32093265 DOI: 10.3390/cells9020487

Regulatory T cells (Tregs) are renowned for maintaining homeostasis and self-tolerance through their ability to suppress immune responses. For over two decades, Tregs have been the subject of intensive research. The immunosuppressive and migratory potentials of Tregs have been exploited, especially in the areas of cancer, autoimmunity and vaccine development, and many assay protocols have since been developed. However, variations in assay conditions in different studies, as well as covert experimental factors, pose a great challenge to the reproducibility of results. Here, we focus on human Tregs derived from clinical samples and highlighted caveats that should be heeded when conducting Tregs suppression and migration assays. We particularly delineated how factors such as sample processing, choice of reagents and equipment, optimization and other experimental conditions could introduce bias into the assay, and we subsequently proffer recommendations to enhance reliability and reproducibility of results. It is hoped that prioritizing these factors will reduce the tendencies of generating false and misleading results, and thus, help improve our understanding and interpretation of Tregs functional studies.

Matched MeSH terms: Autoimmunity
Thyroid autoimmunity and autoimmune thyroid disease in Malaysian girls with Turner syndrome: An understudied population

Lee YL, Zaini AA, Idris AN, Abdullah RA, Wong JS, Hong JS, et al.

J Paediatr Child Health, 2023 Jul;59(7):879-884.
PMID: 37066819 DOI: 10.1111/jpc.16405

AIMS: Knowledge on the spectrum of thyroid disorders amongst Turner syndrome (TS) patients in Southeast Asia is limited. This study aimed to evaluate the prevalence of thyroid autoimmunity, the spectrum of autoimmune thyroid disease and association with age and karyotype amongst Malaysian TS girls.
METHODS: A cross-sectional study was conducted at 11 paediatric endocrine units in Malaysia. Blood samples for antithyroglobulin antibodies, antithyroid peroxidase antibodies and thyroid function test were obtained. In patients with pre-existing thyroid disease, information on clinical and biochemical thyroid status was obtained from medical records.
RESULTS: Ninety-seven TS patients with a mean age of 13.4 ± 4.8 years were recruited. Thyroid autoimmunity was found in 43.8% of TS patients. Nineteen per cent of those with thyroid autoimmunity had autoimmune thyroid disease (Hashimoto thyroiditis in 7.3% and hyperthyroidism in 1% of total population). Patients with isochromosome X and patients with 45,X mosaicism or other X chromosomal abnormalities were more prone to have thyroid autoimmunity compared to those with 45,X karyotype (OR 5.09, 95% CI 1.54-16.88, P = 0.008 and OR 3.41, 95% CI 1.32-8.82, P = 0.01 respectively). The prevalence of thyroid autoimmunity increased with age (33.3% for age 0-9.9 years; 46.8% for age 10-19.9 years and 57.1% age for 20-29.9 years) with autoimmune thyroid disease detected in 14.3% during adulthood.
CONCLUSION: Thyroid autoimmunity was significantly associated with the non 45,X karyotype group, particularly isochromosome X. Annual screening of thyroid function should be carried out upon diagnosis of TS until adulthood with more frequent monitoring recommended in the presence of thyroid autoimmunity.

Matched MeSH terms: Autoimmunity
Islet autoimmunity status in Asians with young-onset diabetes (12-40 years): association with clinical characteristics, beta cell function and cardio-metabolic risk factors

Thai AC, Mohan V, Khalid BA, Cockram CS, Pan CY, Zimmet P, et al.

Diabetes Res Clin Pract, 2008 May;80(2):224-30.
PMID: 18207602 DOI: 10.1016/j.diabres.2007.12.003

In this paper, the islet autoimmunity status and relation to clinical characteristics, beta cell function and cardio-metabolic risk factors in young-onset Asian diabetic patients are evaluated at baseline. The study population consisted of 912 patients (from China, India, Malaysia and Singapore) with age 12-40 years and diabetes duration <12 months. Autoantibodies to glutamic acid decarboxylase (GADA) and tyrosine phosphatase (IA-2A), beta cell function and cardio-metabolic risk parameters were assessed. Among our young patient cohort, 105 (11.5%) patients were GADA and/or IA-2A positives (Ab +ve). Ab +ve patients were younger, leaner, had more severe hyperglycaemia and lower beta cell function. The frequency of metabolic syndrome was significantly lower in Ab +ve patients (27%) compared to Ab -ve patients (54%). However, a substantial proportion of patients in both groups of patients had atherogenic dyslipidaemia, hypertension and albuminuria (micro or macro). In our study cohort, only one in 10 Asian youth with new-onset diabetes had evidence of islet autoimmunity. At least 60% of Ab +ve and 50% of Ab -ve patients demonstrated classical features of type 1 and type 2 diabetes respectively. Regardless of autoimmunity status, the cardio-metabolic risk factors, in particular atherogenic dyslipidaemia, hypertension and albuminuria were common in our patients with young-onset diabetes.

Matched MeSH terms: Autoimmunity*
Fulltext Diabetes-associated autoantibodies among young diabetes mellitus patients in Malaysia

Hasni Mahayidin, Siti Zulaikha Zakariah, Noor Ashidah Ishah, Xu Ann Wee, Masita Arip, Nurhanani Mohamed Nor

Malaysian Journal of Medicine and Health Sciences, 2020;16(2):118-125.
MyJurnal

Introduction: Diabetes-associated autoantibodies (DAA) is the hallmark of T1DM and LADA which are frequently tested in young diabetes patients. It was noted that up to 10-15% of patients with initial diagnosis of T2DM also exhibit DAA. Regardless of the classification, the presence of DAA suggests an underlying islet autoimmunity which lead to progressive pancreatic β-cell failure. There is limited data reported on DAA in young diabetes patients in Malaysia. This study aims to determine the frequency of DAA positivity and its association with demographic and clinical characteristics among this cohort. Methods: A retrospective study using secondary data obtained from Al- lergy and Immunology Research Centre, Institute for Medical Research, Malaysia. This study included 194 diabetes patients who were diagnosed before the age of 40 years old and tested for GADA, ICA, IA2A and IAA. Results: From 194 patients, 91 (46.9%) were positive for least one of the following DAA: ICA (79, 40.7%), GADA (61, 31.4%), IA2A (37, 19.1%) and IAA (9, 4.6%). Multiple positivity was higher (73.6%) compared to single positivity. Highest com- bination of double positivity was ICA+GADA (54, 59.3%) and triple positivity was ICA+GADA+IA2A (25, 27.5%). Simultaneous positivity of four autoantibodies was seen in only one (1.1%) patient. ICA, GADA and IA2A were asso- ciated with age group and ethnicity (all p < 0.001). Only IA2A was associated with gender (p = 0.012). Conclusions: GADA, ICA ad IA2A are more significant in young Malaysian diabetes patients. IAA has a very low frequency in this studied population.

Matched MeSH terms: Autoimmunity
Fulltext Frequency and Manifestations of Autoimmunity Among Children Registered in the Kuwait National Primary Immunodeficiency Registry

Massaad MJ, Zainal M, Al-Herz W

Front Immunol, 2020;11:1119.
PMID: 32582199 DOI: 10.3389/fimmu.2020.01119

Objectives: To present a prospective report on the characteristics of autoimmune manifestations in patients with primary immunodeficient children registered in the Kuwait National PIDs Registry (KNPIDR). Methods: The data were obtained from the Kuwait National Primary Immunodeficiency Disorders Registry during the period of January 2004 to December 2019. Results: A total of 286 PID children were registered in KNPIDR during the study period with a predominance of immunodeficiencies affecting cellular and humoral immunity followed by combined immunodeficiencies with associated syndromic features and diseases of immune dysregulation. Fifty-seven (19.9%) patients presented with a total of 107 autoimmune manifestations. There was no significant statistical association between autoimmune manifestations and gender. Patients with autoimmune manifestations were older at onset of PID symptoms compared to those with no such manifestations, but this did not reach level of significance. The diagnosis delay was longer in patients with autoimmune manifestations compared to those with no such manifestations (p = 0.038). Forty-seven percent of these manifestations were among the presenting symptoms while 53% were documented later during the course of the disease. Fifty-seven percent of the patients developed 1 autoimmune manifestation, 30% developed 2 such manifestations, and 16% had ≥3 autoimmune manifestations. The most common autoimmune manifestation was cytopenia, followed by gastrointestinal manifestations and manifestations of the skin, hair, and nails. Autoimmune cytopenia were more common in patients with immune dysregulation syndromes, while gastrointestinal and skin manifestations predominate in patients with immunodeficiencies affecting cellular and humoral immunity and endocrine manifestations were more common in immune dysregulation syndromes. There were significant statistical associations between developing autoimmune manifestations and death as well as PID categories, being more common in patients with immune dysregulation. The frequency of autoimmunity was high among patients with RAG, WAS, STAT5b, NF-κB2, Fas, FasL, LRBA, APECED, IL-10, and C4 deficiencies. Conclusions: Autoimmunity is frequent in patients with PIDs in Kuwait. This should prompt the suspicion of a PID in patients who present initially with autoimmunity, especially autoimmune cytopenia. Such patients should be managed with extra care since they are at a higher risk of death.

Matched MeSH terms: Autoimmunity
Targeting immunosuppressor cells with nanoparticles in autoimmunity: How far have we come to?

Ahmad S, Al-Hatamleh MAI, Mohamud R

Cell Immunol, 2021 10;368:104412.
PMID: 34340162 DOI: 10.1016/j.cellimm.2021.104412

Autoimmunity is the assault of immune response towards self-antigens, resulting to inflammation and tissue injury. It is staged into three phases and caused by malfunction of immune tolerance. In our body, immune tolerance is synchronized by several immunosuppressor cells such as regulatory T cells and B cells as well as myeloid-derived suppressor cells, which are prominently dysregulated in autoimmunity. Hence, targeting these cell populations serve as a significant potential in the therapy of autoimmunity. Nanotechnology with its advantageous properties is shown to be a remarkable tool as drug delivery system in this field. This review focused on the development of therapeutics in autoimmune diseases utilizing various nanoparticles formulation based on two targeting approaches in autoimmunity, passive and active targeting. Lastly, this review outlined the approved present nanomedicines as well as in clinical evaluations and issues regarding the lack of translation of these nanomedicines into the market, despite the abundant of positive experimental observations.

Matched MeSH terms: Autoimmunity
Fulltext Hide and Seek: The Interplay Between Zika Virus and the Host Immune Response

Lee LJ, Komarasamy TV, Adnan NAA, James W, Rmt Balasubramaniam V

Front Immunol, 2021;12:750365.
PMID: 34745123 DOI: 10.3389/fimmu.2021.750365

Zika virus (ZIKV) received worldwide attention over the past decade when outbreaks of the disease were found to be associated with severe neurological syndromes and congenital abnormalities. Unlike most other flaviviruses, ZIKV can spread through sexual and transplacental transmission, adding to the complexity of Zika pathogenesis and clinical outcomes. In addition, the spread of ZIKV in flavivirus-endemic regions, and the high degree of structural and sequence homology between Zika and its close cousin Dengue have raised questions on the interplay between ZIKV and the pre-existing immunity to other flaviviruses and the potential immunopathogenesis. The Zika epidemic peaked in 2016 and has affected over 80 countries worldwide. The re-emergence of large-scale outbreaks in the future is certainly a possibility. To date, there has been no approved antiviral or vaccine against the ZIKV. Therefore, continuing Zika research and developing an effective antiviral and vaccine is essential to prepare the world for a future Zika epidemic. For this purpose, an in-depth understanding of ZIKV interaction with many different pathways in the human host and how it exploits the host immune response is required. For successful infection, the virus has developed elaborate mechanisms to escape the host response, including blocking host interferon response and shutdown of certain host cell translation. This review provides a summary on the key host factors that facilitate ZIKV entry and replication and the mechanisms by which ZIKV antagonizes antiviral innate immune response and involvement of adaptive immune response leading to immunopathology. We also discuss how ZIKV modulates the host immune response during sexual transmission and pregnancy to induce infection, how the cross-reactive immunity from other flaviviruses impacts ZIKV infection, and provide an update on the current status of ZIKV vaccine development.

Matched MeSH terms: Autoimmunity
Fulltext A plasmid-encoded peptide from Staphylococcus aureus induces anti-myeloperoxidase nephritogenic autoimmunity

Ooi JD, Jiang JH, Eggenhuizen PJ, Chua LL, van Timmeren M, Loh KL, et al.

Nat Commun, 2019 07 29;10(1):3392.
PMID: 31358739 DOI: 10.1038/s41467-019-11255-0

Autoreactivity to myeloperoxidase (MPO) causes anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), with rapidly progressive glomerulonephritis. Here, we show that a Staphylococcus aureus peptide, homologous to an immunodominant MPO T-cell epitope (MPO409-428), can induce anti-MPO autoimmunity. The peptide (6PGD391-410) is part of a plasmid-encoded 6-phosphogluconate dehydrogenase found in some S. aureus strains. It induces anti-MPO T-cell autoimmunity and MPO-ANCA in mice, whereas related sequences do not. Mice immunized with 6PGD391-410, or with S. aureus containing a plasmid expressing 6PGD391-410, develop glomerulonephritis when MPO is deposited in glomeruli. The peptide induces anti-MPO autoreactivity in the context of three MHC class II allomorphs. Furthermore, we show that 6PGD391-410 is immunogenic in humans, as healthy human and AAV patient sera contain anti-6PGD and anti-6PGD391-410 antibodies. Therefore, our results support the idea that bacterial plasmids might have a function in autoimmune disease.

Matched MeSH terms: Autoimmunity/immunology*
Fulltext Clinical Aspects of Janus Kinase (JAK) Inhibitors in the Cardiovascular System in Patients with Rheumatoid Arthritis

Kotyla PJ, Islam MA, Engelmann M

Int J Mol Sci, 2020 Oct 07;21(19).
PMID: 33036382 DOI: 10.3390/ijms21197390

Janus kinase (JAK) inhibitors, a novel class of targeted synthetic disease-modifying antirheumatic drugs (DMARDs), have shown their safety and efficacy in rheumatoid arthritis (RA) and are being intensively tested in other autoimmune and inflammatory disorders. Targeting several cytokines with a single small compound leads to blocking the physiological response of hundreds of genes, thereby providing the background to stabilize the immune response. Unfortunately, blocking many cytokines with a single drug may also bring some negative consequences. In this review, we focused on the activity of JAK inhibitors in the cardiovascular system of patients with RA. Special emphasis was put on the modification of heart performance, progression of atherosclerosis, lipid profile disturbance, and risk of thromboembolic complications. We also discussed potential pathophysiological mechanisms that may be responsible for such JAK inhibitor-associated side effects.

Matched MeSH terms: Autoimmunity/drug effects
IgG4-related disease: features and treatment response in a multi-ethnic cohort in Singapore

Fong W, Liew I, Tan D, Lim KH, Low A, Leung YY

Clin Exp Rheumatol, 2018 05 24;36 Suppl 112(3):89-93.
PMID: 29846168

OBJECTIVES: To describe the features and treatment outcomes of IgG4-RD in multi-ethnic patients in Singapore.
METHODS: Retrospective study was performed on IgG4-RD patients identified from patient databases in a tertiary hospital.
RESULTS: Fourty-two patients (76% male) were included; 79% fulfilled the 2011 comprehensive diagnostic criteria for IgG4-RD for definite IgG4-RD. 81% were Chinese and 19% were Malays. Common initial manifestations included jaundice (52%), abdominal pain (36%) and swollen salivary glands (26%). Only 36% had a history of allergy. 83% had ≥ 1 organ involvement. Erythrocyte sedimentation rate, immunoglobulin E, IgG2 and IgG4 levels were elevated in 84%, 100%, 70% and 44% of patients, respectively. The most common histopathological feature was >10 IgG4+ cells per high power field (66%). 94% (34/36) of patients were treated with moderate to high doses of glucocorticoids, including 17 patients with combination immunosuppressants. Of these, all patients responded to therapy by 3 months. With a median (range) follow-up of 4.1 (0.4-13.8) years, 69% (25/36) needed low dose of glucocorticoids to maintain disease remission. Twenty-six per cent had relapse of disease, of which 82% had disease recurrence in the same organs.
CONCLUSIONS: Pancreatitis, lymphoadenopathy and cholangitis were the commonest manifestations in Asians with IgG4-RD. All patients responded to glucocorticoid therapy by 3 months, two-thirds required maintenance therapy with glucocorticoids, and one-quarter developed relapse of disease.

Matched MeSH terms: Autoimmunity/drug effects*
Rituximab for refractory digital infarcts and ulcers in systemic sclerosis

Khor CG, Chen XL, Lin TS, Lu CH, Hsieh SC

Clin Rheumatol, 2014 Jul;33(7):1019-20.
PMID: 24722688 DOI: 10.1007/s10067-014-2579-1

Systemic sclerosis is an uncommon connective tissue disease characterised by excessive deposition of collagen and vasculopathy which affects the skin and multiple internal organs. It is associated with autoimmunity, inflammation, vasculopathy and fibrosis. Managing Raynaud's phenonemon, digital infarcts and ulcers in systemic sclerosis patients is often a challenge particularly among rheumatologists. We report a case of systemic sclerosis patient with refractory digital infarcts and ulcers responded successfully with rituximab.

Matched MeSH terms: Autoimmunity
Fulltext Challenges in the classification and management of Asian youth-onset diabetes mellitus- lessons learned from a single centre study

Yeow TP, Aun ES, Hor CP, Lim SL, Khaw CH, Aziz NA

PLoS One, 2019;14(1):e0211210.
PMID: 30682116 DOI: 10.1371/journal.pone.0211210

It remains widely perceived that early-onset Type 2 Diabetes (T2D) in children and adolescents is rare and clinically distinct from Type 1 Diabetes (T1D). We studied the challenges of classifying subtypes of early-onset diabetes using clinical features and biomarkers, and management of these patients. We reviewed retrospectively the record of patients < 25 years old who attended the diabetes clinic in Penang General Hospital, Malaysia between 1st December 2012 and 30th June 2015. We examined their clinical features, C-peptide and pancreatic autoantibodies. Comparisons were made between T1D and T2D for magnitude, demographics, metabolic status and complications. We studied 176 patients with a mean age of 20 ± 3.7 years, 43.2% had T1D, 13.6% had T2D, and 13.6% had mixed features of both. When tested, pancreatic autoantibodies were positive in 59.4% of the T1D. T2D presented two years later than T1D at 14.3 years, 20% were asymptomatic at presentation, and 50% required insulin supplementation despite fasting c-peptide of > 250 pmol/L. HbA1C of ≤ 8.0% (64 mmol/mol) was achieved in 30.3% of T1D, 58.3% of T2D on OAD and 16.7% of T2D on insulin. The T2D had greater cardiovascular risk with higher body mass index, more dyslipidaemia, higher blood pressure and earlier onset of nephropathy. The overlapping clinical features, variable autoimmunity, and beta-cell loss complicate classification of young diabetes. Pancreatic autoantibodies and C-peptide did not always predict diabetes subtypes nor respond to insulin. The poor metabolic control and high cardiovascular risk burden among the T2D highlight the need for population-based study and focused intervention.

Matched MeSH terms: Autoimmunity

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