Feasibility of Indirect immunofluorescence (IIF) alone as a screening method for antinuclear antibody in connective diseases in India's sub-Himalayan region

Background: For the management of connective tissue disorders (CTDs), antinuclear antibody (ANA) testing is essential, both from diagnostic and prognostic points of view. Usually, patterns obtained by ANA-IIF testing correlates to specific autoantibodies as obtained from the test for ENA (by LIA/ELISA, etc.). But to apply these data from western studies, we may need validation in the local population like our subjects in sub-Himalayan (Garhwal region) area where CTDs are common. Also, suppose ANA-IFA pattern's correlation is reliably known in our population, it can minimize the cost of managing CTDs by limiting ENA testing, which is 10 times costlier than ANA-IIF. Hence, this study was undertaken to know the specific autoantibody targets (ENA by LIA) against ANA-IIF patterns in our local population. Materials and Methods: In this retrospective cross-sectional work, serum samples of CTDs were tested for ANA by IIF (Euroimmune AG) and ENA by LIA (Euroline ANA-3G) continuously for 36 months. The manufacturer's kit insert was followed, and results were analyzed applying appropriate statistical methods. Results: Major ANA-IIF patterns were found to be associated with specific autoantibodies, for example, Nuclear homogenous with dsDNA, nucleosomes, histones; speckled pattern with nRNP/Sm, Sm, SSA/Ro-52, SSB; nucleolar pattern with Scl-70, Pm-Scl 100 and centromere pattern with CENP-B. Anticytoplasmic (ACA) are found to be linked with some ANA negative (by IIF) samples, emphasizing the need for careful observation for ACA especially where ANA is not found. Conclusions: In most subjects, specific ENA targets correlated well with ANA-IIF patterns, implying effective cost minimization in CTD management. Similar future prospective studies (with clinical data) can provide a database and reference for our population.

The clinical characteristics of nuclear dense fine speckled pattern in 95 289 patients / 中华内科杂志

To investigate the distribution and clinical significance of nuclear dense fine speckled (DFS) pattern in various diseases. A total of 95 289 patients who received DFS tests at Peking Union Medical College Hospital from January 2019 to December 2020 were included in this study. The results of indirect immunofluorescence assay (IIF) for detection of antinuclear antibody (ANA) were evaluated. The positive rates of ANA and DFS were 39.60% (37 733/95 289) and 1.19% (1 139/95 289) respectively. The positive rate of DFS in ANA-positive patients was 3.02% (1 139/37 733). DFS and ANA positivity were significantly different among different age groups rather than gender. The positivity rate of DFS reached the peak (55.57%, 633/1 139) in young patients between 21-40 years, while positive ANA with negative DFS was mainly observed in patients between 41-60 years (37.26%, 13 636/36 594). Additionally, single ANA-positivity were mainly detected in rheumatology department (59.23%, 18 402/31 066), whereas positive DFS was more common in obstetrics and gynecology department (3.08%, 49/1 593). There were 82.88% (944/1 139) patients with positive DFS diagnosed with non-autoimmune disease (non-AID), and 19.49%(222/1 139) with dermatosis. Positive DFS with higher titer (≥1∶320) was detected more frequently in autoimmune disease (AID) patients (5.13%, 10/195) than in non-AID patients (1.69%, 16/944) ( P<0.05). The DFS pattern is rare in ANA positive patients, which is mainly observed in women between 21-49 years. High titer of DFS is prevalent in AID patients, but positive DFS is detected more in non-AID patients, especially those with dermatosis.

Certain Polymorphisms in SP110 Gene Confer Susceptibility to Tuberculosis: A Comprehensive Review and Updated Meta-Analysis

PURPOSE: Numerous studies have assessed the association of SP110 gene variants with tuberculosis (TB), but the results were inconsistent. Through a comprehensive review and meta-analysis, our study aimed to clarify the nature of genetic risks contributed by 11 polymorphisms for the development of TB. MATERIALS AND METHODS: Through searching PubMed, web of science, China National Knowledge Infrastructure (CNKI) databases, a total of 11 articles including 13 independent studies were selected. The pooled odd ratios (ORs) along with their corresponding 95% confidence interval (CI) were estimated for allelic comparisons, additive model (homozygote comparisons; heterozygote comparisons), dominant model and recessive model. We also assessed the heterogeneity across the studies and publication bias. RESULTS: The results of combined analysis revealed a significantly increased risk of TB for single nucleotide polymorphism (SNP) rs9061 in all five comparisons (allelic comparisons: OR=1.28, 95% CI=1.14–1.44, p<0.0001; homozygote comparisons: OR=2.84, 95% CI=1.84–4.38, p<0.00001; heterozygote comparisons: OR=1.23, 95% CI=1.05–1.43, p=0.009; dominant model: OR=1.32, 95% CI=1.14–1.53, p=0.0003; recessive model: OR=2.26, 95% CI=1.18–4.34, p=0.01). In subgroup analysis, the risk of TB associated with SNP rs9061 appeared to be increased. Moreover, increased risk of TB was also found in Asian subgroup of SNP rs11556887, while decreased risk of TB appeared in large sample size subgroup of SNP rs1135791. No significant association was observed between other SNPs and the risk of TB. CONCLUSION: Our meta-analysis suggested that the variant of SNP rs9061 might be a risk factor for TB.

Phacomatosis Pigmentokeratotica / 대한피부과학회지

No abstract available.

Phacomatosis Pigmentokeratotica / 대한피부과학회지

No abstract available.

Bilateral recurrent speckled leukoplakia: a case report

Largely oral cancers are preceded by potentially malignant lesions, which may appear as white or red patches on the oral mucosa. Leukoplakia is one of the most common epithelial precursors of oral squamous cell carcinoma. Speckled leukoplakia is a rare type of leukoplakia with a very high risk of premalignant growth and mortality rate. Though it is the common precancerous lesion, it poses a major diagnostic and therapeutic challenge. We present a rare case of bilateral recurrent speckled leukoplakia with malignant transformation and discuss this relatively rare entity in light of current information from the literature. We also attempt to present the clinical relevance, and the therapeutic modalities available for the management of the disease.

Clinical Significance of Dense Fine Speckled Pattern in Anti-nuclear Antibody Test using Indirect Immunofluorescence Method / 대한진단검사의학회지

BACKGROUND: Dense fine speckled (DFS) pattern in antinuclear antibody (ANA) test using indirect immunofluorescence method became to be known recently and it is detected in patients with various chronic inflammatory diseases as well as in healthy individuals. We investigated the relation between DFS pattern and various diseases. METHODS: ANA tests by indirect immunofluorescence method using HEp-2 cell line slide (Kallestad; Bio-Rad, USA) were performed in 2,654 patients for screening of systemic autoimmune diseases. The frequencies of ANA and DFS positivity were analyzed according to sex, age, clinical department and disease. RESULTS: ANA was positive in 13.3% (352/2,654) of the total patients, and the frequency of DFS pattern was observed in 3.8% (101/2,654) of the total patients and in 28.7% (101/352) of the patients with ANA positivity. Higher frequency of DFS positivity was observed in patients referred from Departments of Rheumatology and Nephrology, but there was no difference in the frequencies of DFS positivity among the patients with ANA positivity. The frequency of DFS pattern was higher in seborrheic dermatitis (14.3%), herpes zoster (11.1%), rheumatoid arthritis (16.9%), systemic lupus erythematosus (15.4%) and Sjogren syndrome (14.3%). CONCLUSIONS: The DFS pattern is a frequent finding (about 28% of ANA positivity) in ANA test using indirect immunofluorescence method. Relatively high frequency of DFS pattern was observed in autoimmune diseases, contrary to the previous observations that DFS pattern is not related with autoimmune diseases. Further studies including the confirmation tests of anti-DFS70 are needed for the identification of relation between DFS pattern and particular diseases.

A Case of Speckled Lentiginous Nevus Showing Histopathologic Features of Congenital Melanocytic Nevus / 대한피부과학회지

Speckled lentiginous nevus is characterized by numerous, small, darkly-pigmented speckles on the background of tanned hyperpigmentation. The tan macule or patch of speckled lentiginous nevus shows the histologic features of lentigo simplex. The speckled areas are characterized by various types of nevi including junctional, compound or dermal nevus. However, since speckled lentiginous nevus may present at birth and show the histologic features of congenital melanocytic nevus (CMN), some have speculated that it is a subtype of CMN. We present a case of speckled lentiginous nevus which occurred at birth and showed histologic features of CMN, thus supporting the notion that speckled lentiginous nevus is a subtype of CMN.

Spitz Nevus in a Giant Speckled Lentiginous Nevus / 대한피부과학회지

Speckled lentiginous nevus is circumscribed patch of hyperpigmentation with smaller, darker pigmented macules or papules within the patch. The background shows histologic features of lentigo simplex. The speckled areas show junctional or compound nevus. Association of speckled lentiginous nevus with multiple spitz nevi was rarely reported. We report a case of multiple spitz nevi arising in a giant speckled lentiginous nevus.

Antinuclear Antibody Production in Patients with Malaria Infection / 대한임상병리학회지

BACKGROUND: Infection can activate the immune system and may trigger the production of autoantibodies. It has been reported that malaria infection triggers the production of various autoantibodies. Therefore, we investigated the pattern and significance of antinuclear antibodies (ANA) found in patients with malaria infection. METHODS: Our study group included 36 patients who were diagnosed with malaria infection at Mokdong Hospital from July 1998 to July 2001. We performed antinuclear antibody test using indirect immunofluorescence method (Quantafluor, Sanofi Diagnostics Pasteur Inc., USA), extractable nuclear antigen test (ENA) using double immunodiffusion method (Nova Gel, Inova Diagnostics Inc., USA), anti-double stranded DNA Ab test (anti-ds DNA Ab) using Farr assay (DPC anti-DNA, Diagnostic products Corporation, USA), and anti-single stranded DNA Ab test (anti-ssDNA Ab) using enzyme immunoassay method (QUANTA, Lite ssDNA, Inova Diagnostics Inc., USA). RESULTS: Among the 36 patients, 32 patients (88.9%) showed ANA positivity and 27 patients (75.0%) showed cytoskeleton or speckled pattern of ANA. Anti-ssDNA Ab was found in 3 of 20 patients; however, anti-dsDNA Ab and ENA were not found in all patients. Patients who had ANA showed higher levels of IgG, IgM and IgA, compared with those patients who did not have ANA. Follow up (11-37 month) of the 13 patients with ANA positivity revealed no symptoms associated with autoimmune disorder. CONCLUSIONS: Malaria infection may develop ANA, especially cytoskeleton or speckled pattern. The follow up of patients with ANA positivity showed no symptoms associated with any autoimmune disorder, but further evaluation would be necessary to reveal the relationship between malaria infection and development of autoimmune disorder.

A Case of Speckled Lentiginous Nevus combined with Spitz Nevi / 대한피부과학회지

Speckled lentiginous nevus(SLN) is characterized by a tan background patch on which more darkly pigmented macules and papules are randomly distributed. The presence of agminated Spitz nevi with SLN is well known, but a solitary Spitz nevus arising on a SLN is rare. We herein report a case of SLN with two Spitz nevi developed individually and congenital melanocytic nevus in a 9-year-old boy.

The Pattern of Epidermal Immune Deposits in Patients with High - Titer Anti - Ro Positive Lupus Erythematosus / 대한피부과학회지

BACKGROUND: Antibodies to Bo antigen are present in most patients with subacute cutaneous lupus erythematosus and in about 50% of Korean patients with systemic lupus erythematosus (LE). However, the pattern of in vivo epidermal deposits of anti Ro antibodies has not been widely recognized. OBJECTIVE: The purpose of thjs study was to define characteristic findings of direct and indirect immunofluorescence(IF) in patients with high-titer anti-Ro or anti-Ro/La positive LE. METHODS: Lupus band test (riirect IF with normal appearing forearm skin specimens) and indi- rect IF with normal skin substr ates were performed with 3 patients of systemic LE who have high titers( >1: 640) of anti-Ro or anti-Ro/La antibodies but have no antibodies against other nuclear antigens such as nDNA/Sm/nRNP/Scl-70. RESULTS: An identical pattern of immune deposits was observed in the epidermis in all 3 pa- tients through direct and indirect, IF examinations. The characteristic pattern recognized was "fine speckling" of IgG (or IgG/IgM) mainly at the nuclei on the basal keratinocytes or keratinocytes throught the epidermis. In the immunoblot assay performed with one patient, IgG anti-Ro/La anti- bodies were identified to recognize the 52/42kD antigens (probably, the Ro/La antigens) in the cultured keratinocyte extracts. CONCLUSION: Most direct IF studies in patients with systemic LE(lupus band test) have shown granular depositions of immunoglabulins and complement components along the dermoepidermal junction, however, the staining patterns as observed in this study may have been overlooked. The recognizable fine speckled patteen of immune deposits at the epidermal keratinocytes could he taken into account as a positivi. finding in the broad category of "lupus band", seen with the normal appearing skin in patient s with systemic LE, especially, who have high titers of anti-Ro/ La antibodies.

A Case of Plexiform Neurofibroma Developed under the Overlying Speckled Lentiginous Nevus

We report a case of plexiform neurofibroma developed under the overlying speckled lentiginous nevus, which occurred in a 20 year-old man. In this patient and his family no other signs of von Recklinghausens disease were found. Discussion is focussed on the fact that both plexiform neurofibroma and speckled lentigmous nevus, which represent a defect in the neural crest, occurred in the same area of the skin.