The high frequency and clinical feature of seronegative myasthenia gravis in Southern China

Anti-acetylcholine receptor antibodies (anti-AChR-Ab) are responsible for the failure of neuromuscular junction in myasthenia gravis (MG). Some anti-AChR-Ab-seronegative MG patients have anti-muscle-specific tyrosine kinase antibodies (anti-MuSk-Ab). Here, the anti-AChR-Ab was tested in 250 MG outpatients from Southern China. While anti-MuSk-Ab was tested in 66 patients who had no anti-AChR-Ab in blood serum, but none of them was positive. The antibodies were measured by a radioimmunoprecipitation assay. The frequency of anti-AChR-Ab was 51.2 %. The percentage of anti-AChR-Ab in ocular type was lower than generalized type (44.9 vs. 66.2 %, P = 0.002). Seronegative MG was characterized by a lower percentage of thymoma than seropositive patients (P = 0.013). It seemed to be less severe in seronegative MG than seropositive MG in these 250 patients. In ocular type, seronegative MG mainly manifesting blepharoptosis but seldom diplopia or eyeball fixation related to ocular movement disability (P = 0.016). While in generalized type, seronegative MG was characterized by a lower percentage of bulbar muscle involvements than seropositive patients (P = 0.005). Logistic regression analysis revealed that bulbar weakness was affected by the existence of anti-AChR antibodies (OR = 3.524, P = 0.015). Besides, seronegative MG tended to be characterized by a lower percentage of neck extensor involvement, but this did not reach significance. The percentage of anti-AChR antibodies was much lower than other countries. Seronegative MG has characteristic clinical features that are different from features of the remaining seropositive MG. This emphasises the predictive value of anti-AChR antibodies analysis in MG patients.     

重症肌无力胸腺切除术后缓解与复发的临床观察

目的探讨伴与不伴胸腺瘤重症肌无力(MG)患者胸腺切除术后预后结局的差异,分析其预后因素。方法收集2017年9月至2018年12月在作者医院行胸腺切除术的MG 67例,比较伴与不伴胸腺瘤MG患者术后不同时间节点理想状态率、复发率的差异,并分析影响预后的因素。结果 (1)非胸腺瘤-MG术后1、6、12个月与胸腺瘤-MG术后6、12个月肌力评分均较术前明显降低(P<0.05)。(2)非胸腺瘤-MG术后理想状态率1个月(5.6%)、6个月(31.1%)、12个月(54.8%)及胸腺瘤-MG术后1个月(0%)、6个月(23.1%)、12个月(42.9%)均逐渐上升,两组间比较无统计学差异。早手术(起病-手术间期<6个月)、眼肌型是MG患者术后达到理想状态的有利因素,OR(95%CI)分别为4.211(1.146~15.475)、4.813(1.430~16.203)。(3)非胸腺瘤-MG术后复发率1个月(3.7%)、6个月(33.3%)、12个月(54.8%)及胸腺瘤-MG术后1个月(30.8%)、6个月(30.8%)、12个月(57.1%)逐渐上升,两组间比较仅第1个月的差异有统计学意义(P<0.05)。手术-复发间隔时间较短者多见于乙酰胆碱受体抗体(AChR-Abs)强阳性(≥20nmol/L)MG及胸腺瘤-MG(P=0.038,P=0.001)。结论对具有一定适应证的MG患者早期行胸腺切除有助于提高理想状态率;AChR-Abs强阳性、胸腺瘤-MG患者术后早期复发风险大;伴或不伴胸腺瘤-MG术后远期预后无统计学差异。     

Antibodies against the main immunogenic region of the acetylcholine receptor correlate with disease severity in myasthenia gravis

Objective We developed an assay that detects autoantibodies against the main immunogenic region (MIR) located at the extracellular end of the nicotinic acetylcholine receptor (AChR) α subunit, and investigated its clinical relevance in myasthenia gravis (MG). Methods In this retrospective cohort study, we measured MIR antibody (Ab) titres in sera obtained before treatment and analysed their associations with clinical parameters in 102 MG patients from two neurological centres. MIR Ab titres were determined using a modified competition immunoprecipitation assay in the presence or absence of monoclonal antibody 35. Results 11 of 23 (47.8%) ocular type and 66 of 72 (91.7%) generalised type MG patients were positive for the presence of MIR Abs, defined as a titre >16.8% (3 SDs above the mean for 70 healthy controls). A significantly higher MIR Ab titre (p<0.001) was shown in generalised type (47.9±19.2%) rather than in ocular type MG patients (16.4±8.4%). Bivariate regression analysis using both titre levels of MIR Ab and routine AChR binding Ab as variables revealed MIR Abs to be an exclusive indicator positively associated with disease severity (Myasthenia Gravis Foundation of America classification, p<0.0001; Quantitative MG score, p=0.008), the presence of bulbar symptoms (p<0.0001) and thymoma (p=0.016), and negatively associated with ocular MG (p<0.0001). Conclusions MIR Ab titre levels show much better correlations with factors related to disease severity compared with AChR binding Ab titres. The MIR Ab assay may be useful for predicting MG symptom severity, especially for discriminating between ocular and generalised types of MG.     

Myasthenia gravis: disease severity and prognosis

Objectives –  To examine myesthenia gravis (MG) severity and long-term prognosis in seronegative, seropositive, and thymoma MG.
Materials and Methods –  Four series of patients were studied retrospectively. Severity and treatment were assessed each year, and muscle antibodies were assayed.
Results –  Seropositive MG patients had a more severe course than seronegative MG patients. MG severity was higher in non-thymectomized compared to thymectomized early-onset MG patients. MG severity did not differ between thymectomized and non-thymectomized late-onset patients. There was no significant difference in MG severity between thymoma and non-thymoma MG patients.
Conclusions –  MG is more severe in seropositive MG patients. With proper treatment, especially early thymectomy, the long-term prognosis is good in seropositive MG patients. The present studies indicate a benefit of thymectomy in early-onset MG, but no dramatic benefit in late-onset MG. Similar MG severity and outcome was seen in thymoma and non-thymoma MG.     

Prognosis of ocular myasthenia in Korea: a retrospective multicenter analysis of 202 patients

OBJECTIVES: The aims of this study were to obtain data on the frequency with which Korean patients with autoimmune myasthenia gravis (MG) present solely with ocular disturbances and progress to develop generalized disease and to identify the prognostic factors associated with secondary generalization. METHODS: We conducted a retrospective multicenter survey in which a total of 376 adult patients who were newly diagnosed with MG from 2000 through 2005 were reviewed for analysis. Patients with ocular MG at the time of symptom presentation (n=202, 53.7%) were divided into two subgroups according to their prognosis: the patients whose disease remained ocular throughout the follow-ups were placed in the OMG-R group, and the patients who progressed to develop generalized disease were placed in the OMG-G group. Clinical characteristics and laboratory findings were compared between the two subgroups. RESULTS: Secondary generalization developed in 47 (23.3%) of the 202 study subjects, mostly within the first 6 months after symptom presentation, while the disease remained ocular throughout the follow-up duration (median 11.8 months) in the remaining 155 patients (76.7%). AChR antibody, abnormal repetitive nerve stimulation tests (RNST) and thymoma were more frequently observed in the patients in the OMG-G group than in those in the OMG-R group (p<0.01 in all). In seropositive cases, the titers of AChR antibody were also significantly higher in the OMG-G group than in the OMG-R group (median, 3.8 nM vs. 6.4 nM; p<0.05). Cox proportional hazards regression analyses showed that early oral prednisolone treatment significantly reduced the risk of secondary generalization (HR, 0.24; 95% CI, 0.11-0.56), whereas abnormal AChR antibody (HR, 5.34; 95% CI, 1.60-17.8) and thymoma (HR, 2.32; 95% CI, 1.21-4.45) were predictive of the development of secondary generalization. CONCLUSIONS: Our findings suggest that several factors, including the AChR antibody, thymoma, early corticosteroid treatment, and possibly latent neuromuscular abnormality revealed by RNST, may have an impact on the risk of developing generalized disease in Korean patients presenting with ocular myasthenia.     

Factors influencing the outcome of transsternal thymectomy for myasthenia gravis

BACKGROUND: Thymectomy is one of the current treatment strategies for patients with myasthenia gravis (MG); however, the selection criteria for surgery remain controversial. METHODS: The demographic data and the surgical results of 168 patients with MG who underwent transsternal thymectomy from June 1986 to December 2000 were retrospectively reviewed. Follow-up information was obtained by review of the hospital records or telephone contact. The postoperative status of MG was assessed at the interval of 1, 3 and 6 months and then annually. The complete remission rate (CRR) between groups was compared. RESULTS: A total of 168 patients, including 69 male patients and 99 female patients, with a mean age of 38.3 years (range 13-80 years), were analyzed. The symptom duration before operations was from 1 to 312 months with a mean of 33.8 months. Complete follow-up information was obtained on 154 patients (91.6%) with a mean follow-up duration of 98.9 months. Complete remission was achieved in 89 of 154 patients (57.8%) and marked clinical improvement in 47 patients (30.5%). Total improvement rate was 88.3%. Seventeen of 24 patients (70.8%) with ocular MG and 18 of 35 patients (51.4%) with thymoma had reached complete remission during the follow-up period. The CRR increased with each consecutive year and reached the plateau in the fourth postoperative year. There was no surgical mortality. The complication rate was 16.6%. Univariate analysis demonstrated that age <35 years old (P = 0.0001), symptom duration before operation <24 months (P = 0.01) and absence of preoperative steroid treatment (P = 0.04) were favorable prognostic factors. Multivariate Cox regression analysis revealed age <35 years old (odds ratio = 3.645, P = 0.001), symptom duration before operation <24 months (2.311, P = 0.041) were favorable prognostic factors for patients having transsternal thymectomy. CONCLUSIONS: Transsternal thymectomy is feasible in the management of patients with MG at all stages with high improvement rate and low surgical morbidity. Those patients aged 35 years or less at operation, with symptoms developed <24 months before operation, may benefit more from thymectomy. MG patients with thymoma did as well as patients without thymoma, and 18 of 35 patients with thymoma had reached complete remission during the follow-up period. Thymectomy seems to be beneficial also for ocular MG.     

重症肌无力免疫病原学研究Ⅰ重症肌无力患者血清免疫学研究

本文用ＥＬＩＳＡ法同步、动态地观测了２８５例ＭＧ患者血清ＡｃｈＲａｂ、ＰｓＭａｂ和ＣＡＥａｂ的变化。实验结果表明ＭＧ患者体内增高的ＡｃｈＲａｂ是ＭＧ发病的主要体液因素。部分血清ＡｃｈＲａｂ阴性ＭＧ患者（１７．５％）的发病可能与血清ＰｓＭａｂ异常有关。另一部分血清ＡｃｈＲａｂ和ＰｓＭａｂ均异常的ＭＧ患者（１２．６％）则可能同时存在骨骼肌神经肌肉接头突触前和突触后的损害。血清ＣＡＥａｂ测定在辅助诊断胸腺瘤方面具有高度的灵敏度和特异性，可作为临床早期诊断胸腺瘤的过筛检查。     

MuSK antibody-positive, seronegative myasthenia gravis in Korea.

Several reports from Western countries suggest differences in the clinical features of patients with muscle specific kinase (MuSK) antibody-positive and -negative seronegative myasthenia gravis (MG). We performed the first survey in Korea of MuSK antibodies, studying 23 patients with acetylcholine receptor (AChR)-antibody seronegative MG. MuSK antibodies were present in 4 (26.7%) of 15 generalized seronegative MG patients and none of 8 ocular seronegative MG patients. All four MuSK positive patients were females, with pharyngeal and respiratory muscle weakness, and required immunosuppressive treatment. However, overall disease severity and age at onset was similar to that of MuSK-negative MG and treatment responses were equally good.     

MuSK-positive myasthenia gravis is rare in the Polish population

Background and purpose:  MuSK-positive myasthenia gravis (MG) is diagnosed in 0–48% of cases with generalized seronegative MG in different populations. The presence of anti-MuSK antibodies generally relates to a severe course and lack of response to thymectomy. We analyzed for the first time the serology and clinical characteristics of MuSK-positive MG in the Polish population.
Methods:  One hundred and fifty-one patients were tested for the presence of anti-AChR and anti-MuSK antibodies: 62 with seronegative MG, including 14 with ocular seronegative MG, 48 age-matched patients with seropositive MG and 41 controls.
Results: All patients with seropositive MG and the disease controls were MuSK-negative. Anti-MuSK antibodies were detected only in four patients with seronegative MG (8.7% of generalized seronegative cases): three women and one man. All four had predominantly bulbar involvement, and underwent thymectomy, with no apparent benefit. All of them improved clinically after immunosuppressive treatment with remissions lasting up to 7 years.
Conclusion: MuSK-positive MG is rare in Polish population accounting for only 8.7% of seronegative cases with generalized MG. This is consistent with emerging evidence for lower MuSK antibodies at more northerly latitudes.     

Characteristics of late-onset myasthenia gravis

An increasing incidence of myasthenia gravis (MG) has been reported in the elderly, but the full clinical ramifications of late-onset myasthenia gravis (LOMG) remain unclear. We describe the clinical features of our cohort of patients with MG with an emphasis on an onset after the age of 50. This was a retrospective analysis of medical records of a cohort of patients followed in two tertiary neuromuscular clinics and comparison of early onset MG (EOMG) versus LOMG. There were 174 patients with a mean age of onset of 55.2?±?19.1?years, and 44 % were women. Late onset of myasthenia gravis after age 50 was reported in 114 patients (66 %). Anti-AChR antibody titers were elevated in 78 % of patients (65 % with EOMG vs. 85 % with LOMG; p?=?0.003), and frequency of elevated titers of anti-MuSK antibodies was similar in both groups (present in 38 % of all tested seronegative patients). Myasthenic crisis was equally common in generalized EOMG and LOMG (13 %). Ocular MG was more common in LOMG compared to EOMG (40 vs. 18 %, p?=?0.021). Diabetes was more prevalent with LOMG (27 vs. 5 %; p?=?0.0002). Overlapping clinical features of EOMG and LOMG are consistent with a continuous clinical spectrum of a single condition, with more frequent occurrence of seropositive and ocular MG with a late onset. A higher burden of comorbidities, such as diabetes mellitus, may warrant a modified approach to treatment of myasthenia in LOMG. However, overall disease severity may not be higher with aging. These observations have implications for design of MG clinical trials and outcomes studies.     

Immunogenetic heterogeneity and associated autoimmune disorders in myasthenia gravis: a population-based survey in the province of Ferrara, northern Italy

Introduction - The well-established relationship between myasthenia gravis (MG) and HLA antigens varies among different ethnic groups. In Caucasians B8 and/or DR3 alleles have been found associated with young MG women without thymoma and with high titres of acetylcholine-receptor antibody (AChR Ab). An increased frequency of haplotype HLA-A3, B7 and/or DR2 has been observed in older MG patients with low AChR Ab levels. So far, there is no convincing evidence for an association between a specific haplotype HLA and ocular MG or MG with thymoma. MG subjects often show other concurrent autoimmune disorders suggesting a more general inherited predisposition to autoimmunity. We performed a community-based study to verify the HLA-A, B, C, DR and DQ profile on ethnically homogeneous MG patients and with the aim to estimate the frequency of concurrent autoimmune diseases and to compare HLA phenotypes to autoimmune status in different MG patients groups. Methods - Forty-seven patients, living in the province of Ferrara, were followed-up in our neurologic department and typed for HLA Antigens. In addition a set of immunological laboratory tests was performed. Results - We found a trend towards an increased B8 and DR3 frequencies in total affected population; an association between B8 allele and early onset of generalized MG sustained by thymic hyperplasia. The DR3 allele is statistically associated with the presence of additional autoimmune disorders. Conclusions - Our data support the hypothesis of a genetically-based heterogeneity of the disease and show an increased prevalence of associate autoimmune conditions in MG patients.     

The epidemiology of myasthenia gravis,Lambert-Eaton myasthenic syndrome and their associated tumours in the northern part of the province of South Holland

We studied the epidemiology of myasthenia gravis (MG) and the Lambert-Eaton myasthenic syndrome (LEMS), and their association with small cell lung carcinoma (SCLC) and thymoma, in a well defined region of the Netherlands. Available data on all the patients with MG, LEMS, thymoma or SCLC living between 1 January 1990 and 31 December 1999 in the northern region of South Holland, with a population of 1.7 million inhabitants, were evaluated. A total of 202 patients with MG (20 with thymoma) and ten patients with LEMS (seven with SCLC) were identified. LEMS was 46 times less prevalent (2.32 x 10(-6)) than MG (106.1 x 10(-6)), whereas the annual incidence rate of LEMS was 14 times lower (0.48 x 10(-6)) than of MG (6.48 x 10(-6)), reflecting the poor survival of LEMS patients with SCLC. SCLC was diagnosed in 1593 patients, seven (0.44 %) of whom developed LEMS. Mean age at diagnosis of SCLC was significantly lower in SCLC patients with LEMS (p = 0.006). A thymoma was diagnosed in 32 patients, of whom the ten patients with MG (31 %) had a younger age at diagnosis of thymoma than the patients without MG (p = 0.27). This study confirms the increasing prevalence of MG over the last few decades as reported by others, and underscores the relative rarity of LEMS. The frequency of LEMS in our patients with SCLC was lower than reported in previous studies. In patients with a SCLC or thymoma, the tumour was diagnosed at younger age in those who had the associated myasthenic syndrome.     

血清乙酰胆碱受体抗体、突触前膜抗体和胸腺瘤相关抗体与重症肌无力发病关系的研究

本研究用ＥＬＩＳＡ法同步、动态地检测了２８５例ＭＧ患者血清乙酰胆碱受体抗体（ＡｃｈＲａｂ）、突触前膜抗体（ＰｓＭａｂ）和胸腺瘤相关抗体（ＣＡＥａｂ）的变化。实验结果表明，ＭＧ患者体内增高的ＡｃｈＲａｂ是ＭＧ发病的主要体液因素。部分血清ＡｃｈＲａｂ阴性ＭＧ患者（１７．５％）的发病，可能与血清ＰｓＭａｂ异常有关。另一部分血清ＡｃｈＲａｂ和ＰｓＭａｂ均异常的ＭＧ患者（１２．６％），则可能同时存在骨骼肌神经肌接头突触前和突触后的损害。血清ＣＡＥａｂ测定在辅助诊断胸腺瘤方面具有高度的灵敏度和特异性，可作为临床早期诊断胸腺瘤的过筛检查。     

Muscle autoantibodies in subgroups of myasthenia gravis patients

Myasthenia gravis (MG) is caused by autoantibodies to the acetylcholine receptor (AChR), but several other muscle autoantibodies have also been identified in patient sera. We studied muscle autoantibodies against AChR, striated muscle tissue sections (SH), titin, citric acid antigen (CA), and ryanodine receptor (RyR) in sera from 146 consecutive MG patients to evaluate whether a single test or several tests together can predict a thymoma. The MG patients were divided into five subgroups; ocular MG, early-onset MG (< 50 years), late-onset MG (≥ 50 years), MG with thymoma, and AChR antibody negative MG. AChR, SH, titin, CA, and RyR antibodies were detected in 85%, 34%, 34%, 25%, and 14% of the MG patients, respectively. For thymoma MG, AChR, SH, titin, CA, and RyR antibodies were detected in 100%, 75%, 95%, 70%, and 70% respectively. SH, titin, CA, RyR antibodies, and computed tomography of the anterior mediastinum have similar sensitivity for thymoma MG. The specificity of RyR, titin, CA, and SH antibodies for thymoma was 70%, 39%, 38%, and 31%, respectively, which is significantly higher for RyR antibodies than for the others. No single muscle antibody assay can predict a thymoma, and a combination of several antibody assays is preferred, although RyR antibody testing alone showed 70% sensitivity and specificity for thymoma MG. SH and CA antibodies provided only little additional information. Received: 23 September 1999, Received in revised form: 6 December 1999, Accepted: 19 January 2000     

Taste disorders in myasthenia gravis: a multicenter cooperative study

Background and purpose: The purpose of the present study was to investigate the prevalence and clinical characteristics of taste disorders in patients with myasthenia gravis (MG). Methods: We studied 371 Japanese patients with MG (127 men and 244 women; mean age, 56.6 ± 16.9 years) consecutively evaluated between May and September 2010 in six neurological centers comprising the East Japan MG Study Group. Ninety‐three patients (25%) had thymoma. We interviewed all patients to determine whether they had taste disorders during the clinical course of MG and then further evaluated the patients with MG, who reported having taste disorders, using a questionnaire. Results: Taste disorders were observed in 16 (4.3%) of the 371 patients with MG. We concluded that taste disorders in 2.4% of patients with MG excluding other factors were associated with MG itself. All patients had thymoma with seropositivity for anti‐acetylcholine receptor antibodies. Thymoma tended to be advanced, and four patients with Masaoka stage IVa required radiation therapy or chemotherapy. Five patients noticed taste disorders 2–3 months before the onset of MG. Sweet taste loss was more common than salty, bitter, and sour taste loss. Conclusions: This was the first systematic survey of taste disorders in patients with MG by a multicenter study. Taste disorders were more common in the present sample of patients with MG than in the general population.     

Clinical and experimental features of MuSK antibody positive MG in Japan

We investigated the presence of antibodies (Abs) against muscle-specific tyrosine kinase (MuSK) in Japanese myasthenia gravis (MG) patients. MuSK Abs were found in 23 (27%) of 85 generalized seronegative MG (SNMG) patients but not in any of the ocular MG patients. MuSK Ab-positive patients were characterized as having female dominance (M:F, 5:18), age range at onset 18 to 72 (median 45) years old, and prominent oculobulbar symptoms (100%) with neck (57%) or respiratory (35%) muscle weakness. Limb muscle weakness was comparatively less severe (52%), thymoma absent. Most patients had good responses to simple plasma exchange and steroid therapy. MuSK IgG from all 18 patients was exclusively the IgG 4 subclass and bound mainly with the MuSK Ig 1–2 domain. Serial studies of 12 individuals showed a close correlation between the variation in MuSK Ab titers and MG clinical severity ( P  = 0.01 by Kruskal–Wallis). MuSK Ab titers were sharply decreased in patients who had a good response to early steroid therapy or simple plasma exchange, but there was no change, or a rapid increase on exacerbation after thymectomy. Measurement of MuSK Ab titers aids in the diagnosis of MG and the monitoring of clinical courses after treatment.     

Follow-up study of myasthenia gravis: evaluation of thymectomy in 300 patients]

From June 1975 to March 1999, 300 patients of myasthenia gravis(MG) have undergone thymectomy. Among these patients, 69 cases were classified as ocular type of MG(including 15 cases with thymoma), and 231 were generalized type of MG(including 86 cases with thymoma). The efficacy of the treatment was investigated by evaluating current patients' life activity, which is classified in 6 groups(Remission, Much Improved, Improved, Unchanged, Worse, and Died). Among the 214 cases without thymoma, Remission was 75, Much Improved was 56, and Improved was 55, namely 86.9% of these cases showed Improved or better. Among 86 cases with thymoma, Remission was 14, Much Improved was 21, and Improved was 32, namely 77.9% of these cases showed Improved or better. We concluded that post-operative outcome of these patients regardless of thymoma were generally satisfactory, but it was necessary to carry out long term careful follow-up.     

Seronegative myasthenia gravis

Of 221 patients with myasthenia gravis, 18.5% had no detectable antibodies to acetylcholine receptor. Seven of 14 patients (50%) with only ocular symptoms for more than 2 years were seronegative, and 25 of 145 (17%) patients with generalized myasthenia were seronegative. The clinical characteristics of seronegative patients did not differ from patients with high antibody titers. No seronegative patient had a thymoma, but that difference did not reach statistical significance. Lack of serum antibodies did not preclude favorable response to thymectomy or plasmapheresis.     

Mature, long-lived CD4+ and CD8+ T cells are generated by the thymoma in myasthenia gravis.

Antibodies to muscle acetylcholine receptors, to other muscle antigens, and to some cytokines are found in the majority of patients with thymic tumors (thymomas) and myasthenia gravis (MG). The role of the tumor in initiating autoimmunity, however, is unclear; in particular, it is not known whether the thymoma exports mature and long-lived T cells, which could provide help for antibody production in the periphery. Here, we quantified recently exported thymic T cells using the approach of measuring episomal DNA fragments [T-cell receptor excision circles (TRECs)], generated by T-cell receptor gene rearrangement. Compared to values in healthy individuals (n = 10) or in patients with late-onset MG (n = 8), TREC levels were significantly raised in both the CD4+ and CD8+ peripheral blood compartments of patients with thymoma and MG (n = 14, p = 0.002 and p = 0.0004 compared to healthy controls) but only in the CD8+ compartment of the three patients with thymoma without MG (p = 0.4 and p = 0.01 for CD4+ and CD8+). TREC levels decreased following thymectomy to values similar to controls but were substantially raised in patients who had developed tumor recurrence (n = 6, p = 0.04 and p = 0.02 for CD4+ and CD8+); this was associated with increased antibodies to interferon-alpha and interleukin-12 in the one case studied serially. Collectively, these results support the hypothesis that the neoplastic thymoma tissue itself can generate and export mature, long-lived T cells and that these T cells reflect the thymic pathology and are likely to be related to the associated autoimmune diseases. The results also provide a new approach for early diagnosis of thymoma recurrence.     

Comparison of the histological and immunohistochemical features of the thymus in young- and elderly-onset myasthenia gravis without thymoma.

We performed histological and immunohistochemical analyses of the removed thymuses from 20 elderly (onset age > 60 years) and 23 young (onset age < 40 years) patients with myasthenia gravis (MG) who tested positive for serum anti-acetylcholine receptor (AChR) antibodies, but who did not have associated thymoma. In the elderly group, nine (45%) patients had accumulations of lymphocytes, indicating an atrophied thymus with loss of the basic structure. The elderly MG patients with atrophied thymic tissues had higher titres of anti-AChR antibody (59.6+/-81.0 nmol/L) than those with adipose infiltration of the thymus alone (20.1+/-20.9 nmol/L). In immunohistochemical studies using image analysis, both young patients and elderly patients with atrophied thymic tissues were found to have significantly higher levels of CD20 than age-matched controls (p < 0.005). Atrophied thymic tissues, often seen immunohistochemically in young MG patients, may also be found in elderly patients, particularly in those with high titres of the anti-AChR antibody, even though adipose infiltration is marked in these patients.