Validation of distinct pathogenic patterns in a cohort of membranoproliferative glomerulonephritis patients by cluster analysis

Abstract Background A novel data-driven cluster analysis identified distinct pathogenic patterns in C3-glomerulopathies and immune complex-mediated membranoproliferative glomerulonephritis. Our aim was to replicate these observations in an independent cohort and elucidate disease pathophysiology with detailed analysis of functional complement markers. Methods A total of 92 patients with clinical, histological, complement and genetic data were involved in the study, and hierarchical cluster analysis was done by Ward method, where four clusters were generated. Results High levels of sC5b-9 (soluble membrane attack complex), low serum C3 levels and young age at onset (13 years) were characteristic for Cluster 1 with a high prevalence of likely pathogenic variations (LPVs) and C3 nephritic factor, whereas for Cluster 2—which is not reliable because of the small number of cases—strong immunoglobulin G staining, low C3 levels and high prevalence of nephritic syndrome at disease onset were observed. Low plasma sC5b-9 levels, decreased C3 levels and high prevalence of LPV and sclerotic glomeruli were present in Cluster 3, and patients with late onset of the disease (median: 39.5 years) and near-normal C3 levels in Cluster 4. A significant difference was observed in the incidence of end-stage renal disease during follow-up between the different clusters. Patients in Clusters 3–4 had worse renal survival than patients in Clusters 1–2. Conclusions Our results confirm the main findings of the original cluster analysis and indicate that the observed, distinct pathogenic patterns are replicated in our cohort. Further investigations are necessary to analyse the distinct biological and pathogenic processes in these patient groups.

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AB0669 PARTICULARITIES OF TUNISIAN FEMALE AXIAL SPONDYLOARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.6203 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1629.2-1629

Author(s):

K. Ben Abdelghani ◽

Y. Gzam ◽

A. Fazaa ◽

S. Miladi ◽

K. Ouenniche ◽

...

Keyword(s):

Ankylosing Spondylitis ◽

Disease Activity ◽

Axial Spondyloarthritis ◽

Activity Index ◽

Age At Onset ◽

Disease Onset ◽

Disease Activity Index ◽

Reactive Protein ◽

Significant Difference ◽

The Mean

Background:Axial spondyloarthritis (ax-SpA) is a chronic rheumatic disease that mainly affects men. However, the female form of ax-SpA remains insufficiently studied.Objectives:The aim of this study was to determine the clinical characteristics, the disease activity and the functional impact of female ax-SpA in comparison with male ax-SpA.Methods:This is a retrospective study including patients diagnosed with ax-SpA fulfilling the criteria of the Assessment of SpondyloArthritis international Society (ASAS) 2009.Clinical parameters, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath ankylosing spondylitis disease activity index (BASDAI) and Bath ankylosing spondylitis functional index (BASFI) were compared between groups of female and male ax-SpA.Results:Two hundred ax-SpA patients were included with 31% of female (n=62) and a mean age of 43,3 ± 11,2 years.The mean age at onset of symptoms was 31,8 ± 8,9 years for women and 25,3 ± 9,1 years for men (p <0,0001). The mean age at diagnosis was 36,4 ± 9,6 years for women and 31,7 ± 10,4 years for men (p = 0,003). Ax-SpA with juvenile onset was noted in 1,7% of women and 12,1% of men (p = 0,02). Male ax-SpA were significantly more smokers (46.8% vs 5.4%; p <0.001). The mean duration of morning stiffness was 11,3 ± 9,2 minutes for women versus 21,6 ± 19,3 minutes for men (p = 0,005).The mean ESR was 42,4 ± 29,8 mm for women and 28,3 ± 23,4 mm for men (p = 0,001). Radiographic sacroiliitis was present in 69,3% of women versus 84,7% of men (p = 0,01). The use of anti-TNF alpha was less frequent in women (29% vs 48,5%; p = 0,01).Our study didn’t found a statistically significant difference in peripheral manifestations, extraarticular manifestations, CRP, BASDAI and BASFI between the two groups.Conclusion:Female ax-SpA seems to have a better prognosis than male with older age in disease onset, less inflammation, less radiographic sacroiliitis and less use of biological treatments.References:[1]Rusman T, et al. Curr Rheumatol Rep. 2018; 20(6).[2]Siar N, et al. Curr Rheumatol Rev. 2019;Disclosure of Interests:None declared

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Calmodulin mutations and life-threatening cardiac arrhythmias: insights from the International Calmodulinopathy Registry

European Heart Journal ◽

10.1093/eurheartj/ehz311 ◽

2019 ◽

Vol 40 (35) ◽

pp. 2964-2975 ◽

Cited By ~ 25

Author(s):

Lia Crotti ◽

Carla Spazzolini ◽

David J Tester ◽

Alice Ghidoni ◽

Alban-Elouen Baruteau ◽

...

Keyword(s):

Age Of Onset ◽

Late Onset ◽

Age At Onset ◽

Poor Response ◽

Response To Therapy ◽

Polymorphic Ventricular Tachycardia ◽

High Prevalence ◽

Neurological Phenotype ◽

Life Threatening ◽

Neurological Features

Abstract Aims Calmodulinopathies are rare life-threatening arrhythmia syndromes which affect mostly young individuals and are, caused by mutations in any of the three genes (CALM 1–3) that encode identical calmodulin proteins. We established the International Calmodulinopathy Registry (ICalmR) to understand the natural history, clinical features, and response to therapy of patients with a CALM-mediated arrhythmia syndrome. Methods and results A dedicated Case Report File was created to collect demographic, clinical, and genetic information. ICalmR has enrolled 74 subjects, with a variant in the CALM1 (n = 36), CALM2 (n = 23), or CALM3 (n = 15) genes. Sixty-four (86.5%) were symptomatic and the 10-year cumulative mortality was 27%. The two prevalent phenotypes are long QT syndrome (LQTS; CALM-LQTS, n = 36, 49%) and catecholaminergic polymorphic ventricular tachycardia (CPVT; CALM-CPVT, n = 21, 28%). CALM-LQTS patients have extremely prolonged QTc intervals (594 ± 73 ms), high prevalence (78%) of life-threatening arrhythmias with median age at onset of 1.5 years [interquartile range (IQR) 0.1–5.5 years] and poor response to therapies. Most electrocardiograms (ECGs) show late onset peaked T waves. All CALM-CPVT patients were symptomatic with median age of onset of 6.0 years (IQR 3.0–8.5 years). Basal ECG frequently shows prominent U waves. Other CALM-related phenotypes are idiopathic ventricular fibrillation (IVF, n = 7), sudden unexplained death (SUD, n = 4), overlapping features of CPVT/LQTS (n = 3), and predominant neurological phenotype (n = 1). Cardiac structural abnormalities and neurological features were present in 18 and 13 patients, respectively. Conclusion Calmodulinopathies are largely characterized by adrenergically-induced life-threatening arrhythmias. Available therapies are disquietingly insufficient, especially in CALM-LQTS. Combination therapy with drugs, sympathectomy, and devices should be considered.

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Characterization of the Clinical and Laboratory Features of Primary and Secondary Antiphospholipid Syndrome in a Cohort of Egyptian Patients

Current Rheumatology Reviews ◽

10.2174/1573397116666200116095734 ◽

2020 ◽

Vol 16 (4) ◽

pp. 304-310 ◽

Cited By ~ 1

Author(s):

Geilan Abd el-Moniem ◽

Kamal El-Garf ◽

Nesreen Sobhy ◽

Sally Elmaghraby

Keyword(s):

Antiphospholipid Syndrome ◽

Age At Onset ◽

Disease Onset ◽

P Value ◽

Significant Difference ◽

Egyptian Patients ◽

Laboratory Features ◽

Systemic Manifestations ◽

Males And Females

Objective: To study the clinical and laboratory features of Antiphospholipid Syndrome (APS) in a cohort of Egyptian patients and compare between primary and secondary type on the basis of clinical and immunological pattern. Patients and Methods: We reviewed the medical records of 148 antiphospholipid syndrome patients following in Rheumatology and Rehabilitation department, Cairo University. Clinical and immunological data were recorded; subsequently, our patients were compared based on the type of APS, patient’s age and sex. Results: The cohort consisted of 148 patients, 135 females (91.2%) and 13 males (8.8%). The mean age at onset was 23.6 ±7.66 years. 28.4% of patients had primary while, 71.6% of patients had secondary APS. : Patients with secondary APS presented more frequently with the following manifestations compared to patients with primary APS: systemic manifestations (56.6% versus 4.8%, P-value: 0.00), venous thrombosis (41.5% versus 19%, P-value: 0.009), cutaneous vasculitis (19.8% versus 4.8%, P-value: 0.023), thrombocytopenia (37.7% versus 11.9%, P-value: 0.002) and hemolytic anemia (28.3% versus 4.8%, P-value: 0.002). On the other hand, total obstetric manifestations were more common in primary APS (92.5% versus 75%, P-value: 0.007). : Juvenile onset APS presented more frequently with systemic (68.8%, p-value: 0.02), neurological (62.5%, p-value: 0.01) and renal manifestations (31.3%, p-value: 0.005). No statistically significant difference was found between males and females in our cohort. Conclusion: APS has broad spectrum manifestations, which may vary according to the patient’s age at disease onset and association with other diseases. Further more, different ethnicities may show different presentations.

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Age at onset as a determinant of presenting phenotype and initial relapse recovery in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458511417479 ◽

2011 ◽

Vol 18 (1) ◽

pp. 45-54 ◽

Cited By ~ 52

Author(s):

M Cossburn ◽

G Ingram ◽

C Hirst ◽

Y Ben-Shlomo ◽

TP Pickersgill ◽

...

Keyword(s):

Multiple Sclerosis ◽

Late Onset ◽

Age At Onset ◽

Disease Onset ◽

Complete Recovery ◽

Population Based ◽

Disease Course ◽

Index Event ◽

Relapsing Remitting ◽

Age Dependent

Background: Age at onset modifies prognosis in multiple sclerosis (MS) and may also exert an effect on the characteristics of disease ignition. Understanding how age influences presentation informs disease management and may allow differentiation of distinct clinical sub-groups. Objectives: To determine the nature of age-specific presentations of relapsing–remitting MS (RRMS) with respect to onset symptoms, gender ratios and index event outcomes. Methods: In a prospective, population-based sample of 1424 patients in South-East Wales we examined associations between age at onset, clinical features and outcome of the onset event, making specific comparisons between paediatric, adolescent and late-onset MS. Results: Age at onset varied significantly between sexes (Male 31.2, Female 29.3, p = 0.002), 0.7% had paediatric onset, 2.7% adolescent onset and 2.8% late-onset MS (>50 years). Optic neuritis was common in younger patients and declined after age 30. Lower limb motor, facial sensory, sexual and sphincteric symptoms rose with age independent of sex and disease course. F:M ratios were highest <16 years of age and declined with increasing age, with a male excess in those over 50. Probability of complete recovery from index event declined with age from 87.4% in the youngest group to 68% in the eldest ( p = 0.009). Conclusions: Age at disease onset in RRMS exerts a significant effect on gender ratios and presenting phenotype, and allows identification of specific clinical sub-groups. In addition, ability to recover from initial relapse declines with age, suggesting accumulation of disability in MS is an age-dependent response to relapse.

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Impact of Gender and Age-at-onset on Clinical and Medical Features of Rheumatoid Arthritis in Western Algerian Population

Zahedan Journal of Research in Medical Sciences ◽

10.5812/zjrms.108918 ◽

2021 ◽

Vol In Press (In Press) ◽

Author(s):

Siheme Ouali ◽

Khalida Zemri ◽

Khedoudja Kanoun ◽

Harir Noria ◽

Feriel Sellam ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Features ◽

Late Onset ◽

Age At Onset ◽

Laboratory Data ◽

Disease Onset ◽

University Hospital ◽

High Rate ◽

Algerian Population ◽

Gender And Age

Background: This study aimed to demonstrate the gender and age-at-onset differences in rheumatoid arthritis (RA) in the western Algerian population and their impacts on patients' clinical features and medical management. Methods: A retrospective cross-sectional study was carried out at the Internal Medicine and Functional Rehabilitation Departments (University Hospital of Sidi-bel-Abbes region) based on medical records of over 306 RA patients diagnosed between 2016 and 2019 according to ACR 1987 criteria. Late-onset RA (LORA) was deﬁned as disease onset at 51 years of age or older. All data were processed and analyzed via SPSS 22.0. Results: We enrolled 306 rheumatoid arthritis patients (85% women) with a mean age-at-onset of 52.47 ± 12.14. Algerian RA women were more at risk of developing type 2 diabetes (P = 0.035), hypertension (P = 0.003), and thyroid disorders (P = 0.05). We did not find any significant relationship between clinical features, laboratory data, and gender. The LORA group comprised 60.5% of our study population with a higher number of comorbidities such as hypertension (P < 0.001), osteoporosis (P = 0.007), and scleroderma (P = 0.014). Nonetheless, we found evidence of an association between positive anti-CCP, RF rate, and age-at-onset (P = 0.001 and P < 0.001, respectively). Conclusions: Algerian RA women with LORA presented a higher prevalence of comorbidities, while Young-onset RA (YORA) was associated with a high rate of RF.

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Late-Onset Famılıal Medıterranean Fever: Sıngle-Center Experıence And Lıterature Revıew

10.21203/rs.2.23028/v1 ◽

2020 ◽

Author(s):

Okan Aydin ◽

Bugra Han Egeli ◽

Huri Ozdogan ◽

Serdal Ugurlu

Keyword(s):

Familial Mediterranean Fever ◽

Mutation Frequency ◽

Late Onset ◽

Disease Onset ◽

Exon 2 ◽

M694v Mutation ◽

Significant Difference ◽

Mediterranean Fever ◽

Group 2 ◽

Group 1

Abstract Introduction: Familial Mediterranean Fever (FMF) is an autoinflammatory disease characterized by recurrent fever and serositis attacks. The disease onset occurs before 20 years of age in 90% of patients. Rarely, the disease onset occurs after 40 years of age. Aim: We aimed to compare the patients with early and late-onset of disease. Methods: We did a retrospective analysis of 2020 patients registered in our FMF center in the years 2008-2017. Patients with disease onset after the age of 40 (Group 1) were collected. The control group (Group 2), disease onset before the age of 20, was randomly selected with twice amount of the study group. Demographic, clinical and genetic data were recorded. Results: Out of 2020 patients, 41 were in group 1 (2.02%). The male to female ratio was 1:1.7 in both groups. The delay of diagnosis was 5.6±5.75 years in group 1, 10.7±12.3 years in group 2. In terms of clinical features, the only significant difference between two groups belonged to fever seen in 26 (63.4%) patients in group 1 and 67 (81.7%) patients in group 2 (p=0,026). M694V mutation frequency was higher in group 2 whereas exon 2 mutation frequency was higher in group 1. The mean colchicine dose in the 6 months was 1.38±0.64 mg in group 1, 1.61±0.47 mg in group 2. Discussion: In patients with late disease onset, the results of decreased mean colchicine dose during the last 6 months, decreased fever ratio, and increased exon 2 mutation frequency might point out to mild disease severity. Keywords: Familial Mediterranean Fever, late-onset, early-onset, MEFV mutation, colchicine

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Effect of Age at Onset on Disease Characteristics in Vitiligo

Journal of Cutaneous Medicine and Surgery ◽

10.2310/7750.2013.12075 ◽

2013 ◽

Vol 17 (4) ◽

pp. 253-258 ◽

Cited By ~ 7

Author(s):

Amrinder J. Kanwar ◽

Rahul Mahajan ◽

Davinder Parsad

Keyword(s):

Early Onset ◽

Late Onset ◽

Statistical Significance ◽

Age At Onset ◽

Positive Family History ◽

Disease Onset ◽

Disease Characteristics ◽

The Difference ◽

Trauma Stress ◽

Distinguishing Features

Background: Vitiligo is a multifactorial disease in which genetic, immunologic, and environmental factors play an important part. Late-onset vitiligo is a poorly defined entity. Materials and Methods: Case records of patients who attended the pigmentary clinic at our institute from January 2001 to December 2010 were reviewed. Patients with a diagnosis of vitiligo were analyzed with respect to their demographic characteristics with special reference to their age at onset. Results: Patients with disease onset after 30 years had a significantly higher association with precipitating factors such as trauma, stress, and drugs in comparison with early-onset vitiligo ( p < .004). However, the difference did not reach statistical significance when these factors were analyzed individually. There was a significantly higher association with other nonautoimmune diseases ( p = .05), a higher incidence of positive family history ( p < .0001), and a higher association with leukotrichia ( p < .002) in late-onset disease. Early-onset nonsegmental vitiligo was associated with a higher incidence of photosensitivity and pruritus compared to early-onset segmental vitiligo. Conclusion: Late-onset vitiligo has certain distinguishing features compared to early-onset vitiligo.

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Reactions of Open-Pollinated Sweet Corn Cultivars to Stewart's Wilt, Common Rust, Northern Leaf Blight, and Southern Leaf Blight

Plant Disease ◽

10.1094/pdis.1998.82.8.939 ◽

1998 ◽

Vol 82 (8) ◽

pp. 939-944 ◽

Cited By ~ 8

Author(s):

J. K. Pataky ◽

L. J. du Toit ◽

P. Revilla ◽

W. F. Tracy

Keyword(s):

Cluster Analysis ◽

Sweet Corn ◽

Morphological Characteristics ◽

Hierarchical Cluster ◽

Leaf Blight ◽

Northern Leaf Blight ◽

Sources Of Resistance ◽

Significant Difference ◽

Southern Leaf Blight ◽

Stewart's Wilt

Over 800 open-pollinated (OP) varieties of sweet corn were grown and named in the century prior to the development of hybrids, but only a few of the historically important OP cultivars exist today. Alleles that could improve disease resistance of modern sweet corn may be present in the OP cultivars still in existence. The objectives of this research were to compare 36 OP sweet corn cultivars to modern commercial hybrids for reactions to Stewart's wilt, common rust, northern leaf blight (NLB), and southern leaf blight (SLB), and to classify the OP cultivars based on phenotypic reactions to these four diseases. Plants were inoculated in 1994, 1995, and 1996 with Erwinia stewartii, Puccinia sorghi, Exserohilum turcicum, or Bipolaris maydis. Symptoms were rated on a whole-plot basis, and ratings were analyzed by analysis of variance (ANOVA). Means were separated by Bayesian least significant difference values. Some of the OP cultivars had phenotypes that were intermediate to moderately resistant to Stewart's wilt, common rust, NLB, or SLB, but none of the cultivars were more resistant than the best commercial hybrids. Distributions of ratings for rust, NLB, and SLB were less disperse for the OP cultivars than for commercial hybrids. Hence, the resistance of modern sweet corn germ plasm to Stewart's wilt, rust, and NLB appears to be greater than that of the OP cultivars. OP cultivars and four standard hybrids were placed into groups based on a hierarchical cluster analysis of disease reactions. The seven groups formed from the cluster analysis of disease ratings were considerably different than those formed from isozyme variation and morphological characteristics. The partial resistance of some cultivars, e.g., Golden Sunshine, Country Gentleman, Stowell's Evergreen, and Red, may be relatively diverse since these cultivars were placed in different groups based on isozyme and morphological variation. OP cultivars with moderate levels of resistance may be sources of resistance alleles not present in commercial hybrids.

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Phenotype heterogeneity in Late-onset Behçet’s syndrome: A cohort from a referral center in China

10.21203/rs.3.rs-26970/v1 ◽

2020 ◽

Author(s):

Jun Zou ◽

Jian-feng Luo ◽

Dan Luo ◽

Yan Shen ◽

Jian-long Guan

Keyword(s):

Cluster Analysis ◽

Late Onset ◽

Disease Onset ◽

Ocular Involvement ◽

Behçet’S Syndrome ◽

Intestinal Lesion ◽

Clinical Variables ◽

Behçet's Syndrome ◽

Behcet’S Syndrome ◽

Behcet's Syndrome

Abstract Objectives To elaluate the demographic, clinical and major organ involvement of patients with late-onset Behçet’s syndrome (BS) in a tertiary centre in China.Methods It was a cross-sectional study of consecutive BS patients in Huadong Hospital of Fudan University between September 2012 and January 2020, we identified 152 late-onset BS patients diagnosed after age of 40 years. We compared clinical variables between patients with disease onset age before and after 40 years. The relative risks (RRs) of clinical variables were calculated between two age groups. Moreover, a hierarchical cluster analysis was conducted according to twenty-nine variables to determine homogeneous subgroups of patients.Results Late-onset BS patients had a higher incidence of intestinal ulcer (late-onset : early-onset, RR 1.47), but a lower incidence of ocular involvement (RR 0.54) and folliculitis (RR 0.46). Female was associated with genital ulcer, erythema nodosum, and arthritis. Four clusters (C1–C4) were formed. C1 (n = 71) the largest cluster, defined as mucocutaneous group. C2 (n = 20), the arthritis group, C3 (n = 39), the gastrointestinal type, all patients presented with intestinal lesion, and five cases with esophageal ulcer. In C4 (n = 22), showing a mixture of uveitis and vascular group, fifteen patients presented with uveitis and eight had vascular lesion, and one cases had central nervous system lesions.Conclusion This is the first cluster analysis to be carried out in a cohort of late-onset BS patients in China. The significantly lower prevalence of folliculitis in late onset BS and the overall milder disease course suggest that testosterone status may influence disease activity.

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Thrombocytosis as a prognostic factor in polymyalgia rheumatica: characteristics determined from cluster analysis

Therapeutic Advances in Musculoskeletal Disease ◽

10.1177/1759720x19864822 ◽

2019 ◽

Vol 11 ◽

pp. 1759720X1986482 ◽

Cited By ~ 3

Author(s):

Keigo Hayashi ◽

Keiji Ohashi ◽

Haruki Watanabe ◽

Ken-Ei Sada ◽

Kenta Shidahara ◽

...

Keyword(s):

Cluster Analysis ◽

Treatment Response ◽

Hierarchical Cluster Analysis ◽

Polymyalgia Rheumatica ◽

Clinical Course ◽

Hierarchical Cluster ◽

Secondary Outcome ◽

Peripheral Arthritis ◽

Significant Difference ◽

Cluster 2

Background: This study aimed to identify the clinical subgroups of polymyalgia rheumatica (PMR) using cluster analysis and compare the outcomes among the identified subgroups. Methods: We enrolled patients with PMR who were diagnosed at Okayama University Hospital, Japan between 2006 and 2017, met the 2012 European League Against Rheumatism/American College of Rheumatology provisional classification criteria for PMR, and were treated with glucocorticoids. Hierarchical cluster analysis using variables selected by principal component analysis was performed to identify the clusters. Subsequently, the outcomes among the identified clusters were compared in the study. The primary outcome was treatment response at 1 month after commencement of treatment. The secondary outcome was refractory clinical course, which was defined as the requirement of additional treatments or relapse during a 2-year observational period. Results: A total of 61 consecutive patients with PMR were enrolled in the study. Their mean age was 71 years, and 67% were female. Hierarchical cluster analysis revealed three distinct subgroups: cluster 1 ( n = 14) was characterized by patients with thrombocytosis (all patients showed a platelet count of >45 × 10⁴/µl), cluster 2 ( n = 38), by patients without peripheral arthritis, and cluster 3 ( n = 9), by patients with peripheral arthritis. The patients in cluster 1 achieved treatment response less frequently than those in cluster 2 (14% versus 47%, p = 0.030). Refractory cases were more frequent in cluster 1 than in cluster 2; however, no significant difference was noted (71% versus 42%, p = 0.06). Conclusions: Thrombocytosis could predict the clinical course in patients with PMR.

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