[Waldenström macroglobulinemia complicated by peripheral neuropathy due to neural infiltration].

A 51-year-old man with the chief complaint of glove- and stocking-type dysesthesia for >3 years was diagnosed with Waldenström's macroglobulinemia (WM) based on IgM-type M-proteinemia, bone marrow infiltration of plasmacytoid B cells, multiple lymphadenopathies, and splenomegaly. A nerve conduction examination suggested demyelinating neuropathy. Serum anti-myelin-associated glycoprotein antibody was negative. Sural nerve biopsy showed myelin thinning, suggesting demyelination. Axonal damage and tumor cell infiltration in the intrafascicular epineurium were also observed. After chemotherapies with rituximab and bendamustine, M-proteinemia and lymphadenopathies disappeared. However, abnormalities in the nerve conduction examination and dysesthesia were only slightly alleviated. As articles describing patients with WM with peripheral nerve infiltration are limited, we report this case with a literature review.

Anti-nuclear matrix protein 2 antibody-positive inflammatory myopathies represent extensive myositis without dermatomyositis-specific rash.

OBJECTIVES: Myositis-specific autoantibodies (MSAs) define distinct clinical subsets of idiopathic inflammatory myopathies (IIMs). The anti-nuclear matrix protein 2 (NXP2) antibody, a MSA detected in juvenile/adult IIMs, has been reported to be associated with a high risk of subcutaneous calcinosis, subcutaneous oedema and internal malignancies. The study aimed to clarify the clinical features of anti-NXP2 antibody-positive IIMs in detail. METHODS: This was a multicentre retrospective observational study on 76 anti-NXP2 antibody-positive patients. The antibody was detected via a serological assay using immunoprecipitation and western blotting. The patients were selected from 162 consecutive Japanese patients with IIMs. RESULTS: The cohort of anti-NXP2 antibody-positive IIMs included 29 juvenile patients and 47 adult patients. Twenty-seven (35.5%) patients presented with polymyositis phenotype without dermatomyositis-specific skin manifestations (heliotrope rash or Gottron sign/papules); this was more common in the adults than children (48.9% vs 15.8%, P < 0.01). Nine (11.8%) patients had subcutaneous calcinosis, and 20 (26.3%) patients had subcutaneous oedema. In addition, the proportion of patients with muscle weakness extending to the distal limbs was high (36 patients [47.4%]) in this cohort. Adult patients had a higher prevalence of malignancy than the general population (age-standardized incidence ratio of malignancies: 22.4). CONCLUSION: Anti-NXP2 antibody-positive IIMs, which include dermatomyositis sine dermatitis, are characterized by atypical skin manifestations and extensive muscular involvement.

A new diagnostic indication device of a biomarker growth differentiation factor 15 for mitochondrial diseases: From laboratory to automated inspection.

Mitochondrial diseases (MDs) are occasionally difficult to diagnose. Growth differentiation factor 15 (GDF15) has been reported as a biomarker useful for not only diagnosing MDs, but also evaluating disease severity and therapeutic efficacy. To enable the measurement of serum GDF15 concentrations at medical institutions, we developed a new latex-enhanced turbidimetric immunoassay (LTIA) as an automated diagnostic indication test for MDs. We also examined the equivalency of specificity and sensitivity in measuring serum GDF15 concentrations between a commercially available enzyme-linked immunosorbent assay (ELISA) kit and a novel LTIA device in patients with MDs, disease controls, and healthy controls. A clinical performance study used a newly developed LTIA device and an existing ELISA kit to measure the concentrations of GDF15 in 35 MD patients, 111 disease controls, and 86 healthy controls. The median (first quartile-third quartile) of serum GDF15 concentrations measured with the LTIA device was significantly higher (P < .001) in MD patients (1389.0 U/mL [869.5-1776.0 U/mL]) than in healthy controls (380.5 U/mL [330.2-471.8 U/mL]); the interquartile ranges did not overlap between MD patients and healthy controls. The areas under the curve in disease and healthy controls were 0.812 (95% confidence interval [CI]: 0.734-0.886) and 0.951 (95% CI: 0.910-0.992), respectively. The automated, high-throughput technology-based LTIA device has definite advantages over the ELISA kit in shorter processing time and lower estimated cost per sample measurement. The LTIA device of GDF15 may be a sufficiently reliable, frontline, diagnostic indicator of individuals with suspected MDs in the general population.

Social buffering enhances extinction of conditioned fear responses by reducing corticosterone levels in male rats.

The presence of an affiliative conspecific reduces stress responses to a wide variety of stimuli, which is termed "social buffering." We previously reported that social buffering in male rats ameliorated behavioral responses, as well as hypothalamic-pituitary-adrenal axis activation, elicited by an auditory conditioned stimulus (CS). In addition, subjects that experienced social buffering did not show stress responses when re-exposed to the CS the next day in the absence of an accompanying rat. However, the mechanisms underlying this enhancement of between-session extinction are poorly understood. In Experiment 1, we compared corticosterone levels at 0, 10, and 15 min after extinction training. Subjects that experienced social buffering had lower corticosterone levels than subjects that trained alone at the end of extinction training. However, corticosterone levels at 10 and 15 min after training were not affected by the experience of social buffering. These results suggest that a lower level of corticosterone during extinction training had an important role in the enhancement of extinction. To directly assess this, in Experiment 2, we manipulated the corticosterone level during extinction training. We found that a subcutaneous injection of corticosterone before extinction training blocked the enhancement of extinction by social buffering. These results demonstrate that the enhancement is caused by a low level of corticosterone during the training. Taken together, we suggest that social buffering enhances extinction of conditioned fear responses by reducing corticosterone levels in male rats.

Mixed pleomorphic lobular and apocrine carcinoma of the breast: A case report suggesting pathogenesis.

Pleomorphic lobular carcinoma (PLC) of the breast is a variant of lobular carcinoma, characterized by loss of E-cadherin expression and high-grade morphologies. Whether the pathogenesis of PLC is in the ductal or the lobular lineage has been discussed. In this report, a case of PLC combined with apocrine carcinoma is presented. Histologically, the tumor showed two distinct carcinoma components: one was a typical apocrine carcinoma, and the other was a pleomorphic invasive lobular carcinoma. The former showed complete membranous expression of E-cadherin, whereas the latter aberrantly expressed it not on the cell membrane, but in the cytoplasm. Both components were triple-negative and strongly positive for GCDFP-15, suggesting apocrine differentiation. The intraductal component showed only a feature of apocrine ductal carcinoma in situ. This case suggests that apocrine carcinoma could be an origin of PLC.

Growth differentiation factor 15 as a useful biomarker for mitochondrial disorders.

OBJECTIVE: The diagnosis of mitochondrial disorders (MDs) is occasionally difficult because patients often present with solitary, or a combination of, symptoms caused by each organ insufficiency, which may be the result of respiratory chain enzyme deficiency. Growth differentiation factor 15 (GDF-15) has been reported to be elevated in serum of patients with MDs. In this study, we investigated whether GDF-15 is a more useful biomarker for MDs than several conventional biomarkers. METHODS: We measured the serum levels of GDF-15 and fibroblast growth factor 21 (FGF-21), as well as other biomarkers, in 48 MD patients and in 146 healthy controls in Japan. GDF-15 and FGF-21 concentrations were measured by enzyme-linked immunosorbant assay and compared with lactate, pyruvate, creatine kinase, and the lactate-to-pyruvate ratio. We calculated sensitivity and specificity and also evaluated the correlation based on two rating scales, including the Newcastle Mitochondrial Disease Rating Scale (NMDAS). RESULTS: Mean GDF-15 concentration was 6-fold higher in MD patients compared to healthy controls (2,711 ± 2,459 pg/ml vs 462.5 ± 141.0 pg/mL; p < 0.001). Using a receiver operating characteristic curve, the area under the curve was significantly higher for GDF-15 than FGF-21 and other conventional biomarkers. Our date suggest that GDF-15 is the most useful biomarker for MDs of the biomarkers examined, and it is associated with MD severity. INTERPRETATION: Our results suggest that measurement of GDF-15 is the most useful first-line test to indicate the patients who have the mitochondrial respiratory chain deficiency.

Social buffering ameliorates conditioned fear responses in female rats.

The stress experienced by an animal is ameliorated when the animal is exposed to distressing stimuli along with a conspecific animal(s). This is known as social buffering. Previously, we found that the presence of an unfamiliar male rat induced social buffering and ameliorated conditioned fear responses of a male rat subjected to an auditory conditioned stimulus (CS). However, because our knowledge of social buffering is highly biased towards findings in male subjects, analyses using female subjects are crucial for comprehensively understanding the social buffering phenomenon. In the present studies, we assessed social buffering of conditioned fear responses in female rats. We found that the estrus cycle did not affect the intensity of the rats' fear responses to the CS or their degree of vigilance due to the presence of a conspecific animal. Based on these findings, we then assessed whether social buffering ameliorated conditioned fear responses in female rats without taking into account their estrus cycles. When fear conditioned female rats were exposed to the CS without the presence of a conspecific, they exhibited behavioral responses, including freezing, and elevated corticosterone levels. By contrast, the presence of an unfamiliar female rat suppressed these responses. Based on these findings, we conclude that social buffering can ameliorate conditioned fear responses in female rats.

The strain of an accompanying conspecific affects the efficacy of social buffering in male rats.

Social buffering is a phenomenon in which stress in an animal is ameliorated when the subject is accompanied by a conspecific animal(s) during exposure to distressing stimuli. We previously reported that in male Wistar rats, the presence of another Wistar rat mitigates conditioned fear responses to an auditory conditioned stimulus (CS). Subsequent analyses revealed several characteristics of this social buffering of conditioned fear responses. However, information regarding the specificity of accompanying conspecifics is still limited. In the present study, we assessed whether rats of other strains could induce social buffering in Wistar rats. When a fear-conditioned Wistar subject was re-exposed to the CS alone, we observed increased freezing and decreased investigation and walking, as well as elevated corticosterone levels. The presence of a Wistar, Sprague-Dawley, or Long-Evans rat blocked these responses, suggesting that social buffering was induced by these strains of rats. In contrast, a Fischer 344 rat did not induce social buffering in the Wistar subject. We further found that an inbred Lewis rat induced social buffering whereas a Brown Norway rat, a strain that has been established independently from Wistar rats, did not. These results suggest that the difference in origin, rather than the inbred or outbred status of the associate rat, seemed to account for the lack of social buffering induced by the F344 rats. Based on these findings, we conclude that strains of an accompanying conspecific can affect the efficacy of social buffering in rats.

Nivolumab-induced chronic inflammatory demyelinating polyradiculoneuropathy mimicking rapid-onset Guillain-Barré syndrome: a case report.

Nivolumab, an anti-programmed death-1-specific monoclonal antibody, has demonstrated a durable response and effect on overall survival and has become one of the standard treatments for patients with advanced melanoma. Reported herein is a case of nivolumab-induced chronic inflammatory demyelinating polyradiculoneuropathy, in which an 85-year-old woman with stage IV melanoma developed grade 1 paresthesia 2 weeks after the initial dose of nivolumab was administered. With continued treatment, the neurological deficiency deteriorated rapidly, mimicking Guillain-Barré syndrome, causing such a dramatic decrease in her activities of daily living that she could no longer function in daily life. Thus, nivolumab treatment was discontinued. A course of intravenous immunoglobulin infusion yielded a dramatic clinical improvement; in particular, improved motor control was observed within a few days. Her initial presentation was suggestive of acute inflammatory demyelinating polyradiculoneuropathy, a subtype of Guillain-Barré syndrome; however, the good response to steroids and exacerbation 8 weeks after the onset were suggestive of chronic inflammatory demyelinating polyradiculoneuropathy induced by nivolumab. This is the first case of Guillain-Barré syndrome-like autoimmune polyradiculoneuropathy induced by programmed death-1/programmed death-ligand 1 inhibitors. Although neurological adverse events related to nivolumab are rare, they can become severe, requiring early diagnosis and intervention. Intravenous immunoglobulin may be considered as an effective initial treatment for patients who develop acute autoimmune nervous system disorders due to nivolumab.

Skeletal muscle-specific HMG-CoA reductase knockout mice exhibit rhabdomyolysis: A model for statin-induced myopathy.

HMG-CoA reductase (HMGCR) catalyzes the conversion of HMG-CoA to mevalonic acid (MVA); this is the rate-limiting enzyme of the mevalonate pathway that synthesizes cholesterol. Statins, HMGCR inhibitors, are widely used as cholesterol-reducing drugs. However, statin-induced myopathy is the most adverse side effect of statins. To eludicate the mechanisms underlying statin the myotoxicity and HMGCR function in the skeletal muscle, we developed the skeletal muscle-specific HMGCR knockout mice. Knockout mice exhibited postnatal myopathy with elevated serum creatine kinase levels and necrosis. Myopathy in knockout mice was completely rescued by the oral administration of MVA. These results suggest that skeletal muscle toxicity caused by statins is dependent on the deficiencies of HMGCR enzyme activity and downstream metabolites of the mevalonate pathway in skeletal muscles rather than the liver or other organs.

Systematic Asymmetric Synthesis of All Diastereomers of (-)-Talaumidin and Their Neurotrophic Activity.

(-)-Talaumidin (1), a 2,5-biaryl-3,4-dimethyltetrahydrofuran lignan isolated from Aristolochia arcuata Masters, shows significant neurite-outgrowth promotion and neuroprotection in primary cultured rat cortical neurons and in NGF-differentiated PC12 cells. The four stereogenic centers on the tetrahydrofuran moiety in 1 result in the presence of seven diastereomers except for their enantiomers. In order to investigate the stereochemistry-activity relationships of the stereoisomers, the systematic synthesis of all stereoisomers of 1 was accomplished by employing Evans aldol, diastereoselective hydroboration, reductive deoxygenation, and Mitsunobu reactions as key steps. The ability of all of the synthesized stereoisomers to promote neurite-outgrowth in PC12 and neuronal cells was evaluated. All stereoisomers exhibited moderate to potent neurotrophic activities in NGF-differentiated PC12 cells at 30 µM and in primary cultured rat cortical neuronal cells at 0.01 µM. In particular, 1e bearing all cis substituents resulted in the most potent neurite-outgrowth promotion.

Stilbene analogs of resveratrol improve insulin resistance through activation of AMPK.

Resveratrol (RSV), 3,5,4'-trihydroxy-trans-stilbene, is known to have many beneficial physiological activities. We have synthesized several stilbene analogues and have reported that the hydroxyl group in the 4' position of RSV exhibited strong radical scavenging action. Using stilbene analogs, we investigated the structure of RSV to explain its protective effect against obesity and type 2 diabetes. All six analogs used in this study inhibited the differentiation of 3T3-L1 adipocytes. 3-Hydroxy-trans stilbene (3(OH)ST), and 3,4'-dihydroxy-trans stilbene (3,4'(OH)2ST) increased glucose uptake and induced adenosine monophosphate kinase (AMPK) phosphorylation in C2C12 myotubes independently of insulin. An in vivo study using mice fed high-fat diets indicated that 3(OH)ST was more effective than RSV in improving insulin resistance. In conclusion, RSV and its derivatives, particularly 3(OH)ST, inhibited adipocyte differentiation and enhanced glucose uptake in the myotubes, resulting in a reduction of obesity and an improvement in glucose tolerance in vivo.

Large Maf transcription factor family is a major regulator of fast type IIb myofiber determination.

Myofibers are broadly characterized as fatigue-resistant slow-twitch (type I) fibers and rapidly fatiguing fast-twitch (type IIa/IIx/IIb) fibers. However, the molecular regulation of myofiber type is not entirely understood; particularly, information on regulators of fast-twitch muscle is scarce. Here, we demonstrate that the large Maf transcription factor family dictates fast type IIb myofiber specification in mice. Remarkably, the ablation of three large Mafs leads to the drastic loss of type IIb myofibers, resulting in enhanced endurance capacity and the reduction of muscle force. Conversely, the overexpression of each large Maf in the type I soleus muscle induces type IIb myofibers. Mechanistically, a large Maf directly binds to the Maf recognition element on the promoter of myosin heavy chain 4, which encodes the type IIb myosin heavy chain, driving its expression. This work identifies the large Maf transcription factor family as a major regulator for fast type IIb muscle determination.

Characteristics of hypersomnia due to inflammatory demyelinating diseases of the central nervous system.

Background: Neuromyelitis optica spectrum disorder (NMOSD) diagnostic criteria for inflammatory demyelinating central nervous system diseases included symptomatic narcolepsy; however, no relevant case-control studies exist. We aimed to examine the relationship among cerebrospinal fluid orexin-A (CSF-OX) levels, cataplexy and diencephalic syndrome; determine risk factors for low-and-intermediate CSF-OX levels (≤200 pg/mL) and quantify hypothalamic intensity using MRI. Methods: This ancillary retrospective case-control study included 50 patients with hypersomnia and 68 controls (among 3000 patients) from Akita University, the University of Tsukuba and community hospitals (200 facilities). Outcomes were CSF-OX level and MRI hypothalamus-to-caudate-nucleus-intensity ratio. Risk factors were age, sex, hypersomnolence and MRI hypothalamus-to-caudate-nucleus-intensity ratio >130%. Logistic regression was performed for the association between the risk factors and CSF-OX levels ≤200 pg/mL. Results: The hypersomnia group (n=50) had significantly more cases of NMOSD (p<0.001), diencephalic syndrome (p=0.006), corticosteroid use (p=0.011), hypothalamic lesions (p<0.023) and early treatment (p<0.001). No cataplexy occurred. In the hypersomnia group, the median CSF-OX level was 160.5 (IQR 108.4-236.5) pg/mL and median MRI hypothalamus-to-caudate-nucleus-intensity ratio was 127.6% (IQR 115.3-149.1). Significant risk factors were hypersomnolence (adjusted OR (AOR) 6.95; 95% CI 2.64 to 18.29; p<0.001) and MRI hypothalamus-to-caudate-nucleus-intensity ratio >130% (AOR 6.33; 95% CI 1.18 to 34.09; p=0.032). The latter was less sensitive in predicting CSF-OX levels ≤200 pg/mL. Cases with MRI hypothalamus-to-caudate-nucleus-intensity ratio >130% had a higher rate of diencephalic syndrome (p<0.001, V=0.59). Conclusions: Considering orexin as reflected by CSF-OX levels and MRI hypothalamus-to-caudate-nucleus-intensity ratio may help diagnose hypersomnia with diencephalic syndrome.

Gender differences in the association between HDL cholesterol and the progression of diabetic kidney disease in type 2 diabetic patients.

BACKGROUND: The impact of serum lipid abnormalities on the progression of diabetic kidney disease (DKD) remains conflicting. Furthermore, gender differences in the association between dyslipidaemia and outcome of DKD are largely unknown. We therefore conducted this single-centre observational cohort study to clarify gender differences in the association between serum lipid profiles and the progression of DKD. METHODS: Seven hundred and twenty-three Japanese type 2 diabetes mellitus (T2DM) patients with normoalbuminuria or microalbuminuria, 280 women and 443 men, with a mean (± SD) age of 63 ± 11 years were studied. The endpoint was the progression to a more advanced stage of albuminuria. For statistical analyses, Cox proportional hazard model analyses were conducted. RESULTS: During the mean follow-up period of 4.3 years, 62 of 477 patients with normoalbuminuria and 69 of 246 patients with microalbuminuria reached the endpoint. A significant interaction between high-density lipoprotein (HDL) cholesterol and gender was detected (P(interaction) = 0.04); therefore, separate analyses were conducted for men and women. Overall, in men, the univariate Cox proportional hazard model revealed that higher triglycerides and lower HDL cholesterol levels were significantly associated with higher risk of reaching the endpoint. In the multivariate Cox proportional hazard model, only HDL cholesterol levels remained as an independent predictor of the endpoint (hazard ratio 0.391, P = 0.01). In women, no serum lipid parameters were associated with the endpoint. CONCLUSIONS: Lower HDL cholesterol levels seem to be associated with the progression of DKD in men but not in women.

Reduced CSF orexin levels in rats and patients with systemic inflammation: a preliminary study.

OBJECTIVE: Sepsis is a lethal condition characterized by systemic inflammation and multiple organ failure; this condition was initially defined as systemic inflammatory response syndrome (SIRS) due to infection. We previously reported that the hypothalamic neuropeptide orexin improved survival in a murine model of sepsis by mainly acting in the medullary raphe nucleus through orexin type-2 receptors. We hypothesized that orexin treatment enhances recovery from sepsis by reversing the reduction in orexin levels in the cerebrospinal fluid (CSF). We recently reported a case in which CSF orexin levels were reduced in a patient with sepsis. Herein, we attempted to further investigate CSF orexin levels in rats and patients with systemic inflammation. This patient study was a single-center, retrospective observational study. RESULTS: CSF orexin levels were low in rats with lipopolysaccharide-induced systemic inflammation. We enrolled 14 patients with meningitis/encephalitis. Six patients were diagnosed with SIRS, of whom 5 patients had infections ("sepsis" by the previous definition). CSF orexin levels were low in SIRS patients. The results support the hypothesis that orexin treatment enhances recovery from sepsis by reversing the reduction in CSF orexin levels.

Predictive value of ductal carcinoma in situ with invasive breast cancer in core needle biopsies for final pathologic size of intraductal elements.

Preoperative evaluations of the size of ductal carcinoma in situ (DCIS) extension in invasive breast cancer (IBC) are problematic and markers of the actual size of DCIS remain elusive. This study aimed to quantify DCIS on core needle biopsy (CNB) and investigated its association with degree of DCIS extension on paired resection specimens, instead of with presence or absence of an extensive intraductal component or margin status as in earlier studies. This series examined 150 IBCs diagnosed from paired CNB and resection specimens. The DCIS/invasion ratio was calculated using the sum of each element size from CNB. In resection specimens, cases in which the greatest dimension of DCIS extension was longer than the greatest dimension of invasive size were defined as extended DCIS (Ext-DCIS). DCIS/invasion ratio level correlated positively with the degree of Ext-DCIS (P = 0.003). Using receiver operating characteristic curve analysis, setting cases with the subgroup of DCIS extension with greatest dimension > 2.5 times that of the invasive size in the resection specimen (Ext-DCIS > 2.5) as the positive class provided the best discrimination ability for DCIS/invasion ratio (0.375). In multivariate analysis, DCIS/invasion ratio > 0.375 was significantly associated with Ext-DCIS > 2.5 (P = 0.033). In conclusion, DCIS/invasion ratio > 0.375 in CNB was identified as a predictor of Ext-DCIS > 2.5 in resection specimens, suggesting that an approach combining DCIS/invasion ratio from CNB with preoperative staging may better predict the extent of DCIS and facilitate better surgical planning.

p62/Sqstm1 rescue in muscle retards the progression of steatohepatitis in p62/Sqstm1-null mice fed a high-fat diet.

Introduction: Obesity is a risk factor for many diseases because it leads to a reduction in skeletal muscle mass and promotes insulin resistance. p62/Sqstm1-knockout mice are a model of metabolic syndrome; show obesity, insulin resistance, and non-alcoholic fatty liver (NAFL); and develop non-alcoholic steatohepatitis (NASH) in response to the feeding of a high-fat diet (HFD). These phenotypes suggest that muscle p62 may prevent obesity-induced muscle dysfunction. In the present study, we aimed to determine the effects of muscle p62 on skeletal muscle mass, muscle strength, insulin resistance, and NASH pathology. Methods: We generated muscle-specific p62 gene rescue mice (p62-mRes), which express p62 only in muscle and were derived from p62-knock out mice (p62 KIKI ) using the cre/loxp system. p62 KIKI and p62-mRes mice were fed an HFD for 20 weeks and their phenotypes were compared. Results: HFD-feeding caused severe obesity in both p62 KIKI and p62-mRes mice, but there was no effect of muscle p62 on body mass. Limb skeletal muscle mass, grip strength, and the cross-sectional area of muscle fibers were higher in p62-mRes mice than in p62 KIKI . The glucose tolerance and insulin sensitivity of the p62-mRes mice were also superior. The protein expression of mechanistic target of rapamycin, which promotes muscle protein synthesis, and GLUT4, a glucose transporter in skeletal muscle, were higher in the p62-mRes mice. p62 KIKI mice developed severe NASH when fed an HFD, but the progression of NASH was retarded by p62 gene rescue in muscle, and the expression of Tgf-ß1, which encodes a factor that promotes hepatic fibrosis, was reduced. Conclusion: Rescue of muscle-specific p62 in the whole-body p62 knock-out mice ameliorates the insulin resistance and retards the progression of NASH caused by systemic p62 ablation.

Reliability of antinuclear matrix protein 2 antibody assays in idiopathic inflammatory myopathies is dependent on target protein properties.

A line blotting assay (LB) is currently used to detect myositis-specific autoantibodies (MSAs) in patients with idiopathic inflammatory myopathies (IIMs), because of its simplicity; however, the sensitivity and specificity of this assay is low. The aim of this study is to evaluate the accuracy of the commercial LB in detection of antinuclear matrix protein 2 (NXP2) antibody. Seventy-seven serum samples from patients with IIMs, in which anti-NXP2 antibodies were detected through immunoprecipitation and western blotting (IP-WB) using K562 cell lysate, were enrolled. All samples were assessed by LB and IP-WB using recombinant human NXP2 whole protein (rNXP2) produced by insect cells, and the positive rates of each assay were compared. Thirty-two samples (41.6%) showed false-negativity by LB, which includes 11 samples with negative results by IP-WB using rNXP2. Relative intensities of IP-WB using cell lysate were significantly higher in the samples with positive results by both LB and IP-WB using rNXP2, compared to samples with positive by IP-WB using rNXP2 but negative by LB. Three of 11 samples with negative results by both LB and IP-WB using rNXP2 revealed high antibody titers. Further, differences in post-transcriptional SUMOylation were observed between recombinant and natural NXP2 proteins. In conclusion, the LB showed low sensitivity for detection of anti-NXP2 antibody, an effect exacerbated at low titers of anti-NXP2 antibodies. Moreover, there appears to be differences in the reactivities of antibodies to recombinant and natural NXP2 proteins with different post-transcriptional modifications.