Analysis of clinical and pathological characteristics of scleromyositis patients with positive anti-Ku or anti-PM-Scl antibodies

doi:10.3969/j.issn.1672-6731.2023.09.004

Abstract

Abstract:

Objective: To summarize the clinical manifestations and histopathological characteristics of skeletal muscle in scleromyositis patients with positive anti-Ku or anti- PM -Scl antibodies. Methods and Results: Retrospective collection of clinical data from 70 scleromyositis patients diagnosed at Peking University First Hospital from January 2010 to March 2023, analysis showed the average onset age of patients was 36.00 (20.75, 51.25) years old. The initial symptoms of 77.14% (54/70) patients was mainly in the proximal limbs myasthenia [74.29% (52/70)], mild to moderate [77.14% (54/70)], and 52.86% (37/70) patients had systemic symptoms such as fatigue or skin involvement during the course of the disease. The serum creatine kinase (CK) level was 2775.00 (995.50, 4995.75) U/L. About 32.86% (23/70) were positive for anti - Ku antibody, 65.71% (46/70) were positive for anti - PM - Scl antibody, 1.43% (1/70) were both positive, and 27.14% (19/70) could also had increased level of other myositis antibodies. The main histopathological changes were inflammatory [41.43% (29/70)] or necrotic [24.29% (17/70)] myopathic pathological changes, presenting as muscle fiber atrophy [91.43% (64/70)], necrosis [68.57% (48/70)] or regeneration [85.71% (60/70)]. Comparison of symptoms, signs and histopathological characteristics of skeletal muscle between patients with positive anti - Ku antibody and with positive anti - PM - Scl antibody, female proportion (χ²=4.381, P=0.036) and C5b9 deposition damage (χ²=4.725, P=0.030) were higher in the former than those in the latter. Conclusions: Scleromyositis patients with positive anti-Ku or anti-PM -Scl antibodies mostly started in young and middle age, mainly manifesting as mild to moderate myasthenia in the proximal limbs, and skeletal muscle inflammatory or necrotic myopathic lesions as characteristic pathological changes. Compared with positive anti - PM - Scl antibody patients, positive anti - Ku antibody scleromyositis patients were mainly female, and skeletal muscle complement deposition was more notable.

Key words: Myositis, Scleroderma, systemic, Antibodies, Muscle weakness, Pathology, Immunohistochemistry

摘要：

目的: 总结抗Ku或抗PM-Scl抗体阳性硬化性肌炎患者临床表现及骨骼肌组织病理学特征。方法与结果: 回顾分析2010年1月至2023年3月北京大学第一医院明确诊断的70例硬化性肌炎患者临床资料，中位发病年龄36.00(20.75，51.25)岁，77.14%(54/70)以肌无力首发，且以四肢近端肌无力为主[74.29%(52/70)]，多呈轻至中度[77.14%(54/70)]；52.86%(37/70)病程中伴疲劳感、皮肤受累等全身症状；血清肌酸激酶中位值为2775.00(995.50，4995.75)U/L，32.86%(23/70)抗Ku抗体阳性、65.71%(46/70)抗PM-Scl抗体阳性、1.43%(1/70)二者皆阳性，27.14%(19/70)同时合并其他肌炎抗体阳性。组织病理改变以炎症性[41.43%(29/70)]或坏死性[24.29%(17/70)]肌病样改变为主，呈肌纤维萎缩[91.43%(64/70)]、坏死[68.57%(48/70)]和再生[85.71%(60/70)]。抗Ku抗体阳性与抗PM -Scl抗体阳性患者症状与体征以及骨骼肌组织病理学特征比较，抗Ku抗体阳性患者女性(χ²=4.381，P=0.036)和补体C5b9沉积(χ²=4.725，P=0.030)比例高于抗PM-Scl抗体阳性患者。结论: 伴抗Ku或抗PM-Scl抗体阳性硬化性肌炎患者多于中青年期发病，表现为四肢近端轻至中度肌无力，骨骼肌炎症性或坏死性肌病样损害为特征性病理改变；与抗PM-Scl抗体阳性患者相比，抗Ku抗体阳性硬化性肌炎患者以女性居多且骨骼肌补体沉积更为明显。

关键词: 肌炎, 硬皮病, 系统性, 抗体, 肌无力, 病理学, 免疫组织化学

Xin-yu ZHANG, Ya-wen ZHAO, Wei ZHANG, Zhao-xia WANG, Yun YUAN. Analysis of clinical and pathological characteristics of scleromyositis patients with positive anti-Ku or anti-PM-Scl antibodies[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2023, 23(9): 789-797.

张歆雨, 赵亚雯, 张巍, 王朝霞, 袁云. 伴抗Ku或抗PM-Scl抗体阳性硬化性肌炎临床及病理学特征分析[J]. 中国现代神经疾病杂志, 2023, 23(9): 789-797.

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Figures/Tables 7

Table 1. Comparison of general data in patients between anti - Ku antibody positive group and anti - PM - Scl antibody positive group

观察指标	抗Ku抗体阳性组(n = 23)	抗PM-Scl抗体阳性组(n = 46)	χ²或Z值	P值
性别[例(%)]			4.381	0.036
男性	5(21.74)	22(47.83)
女性	18(78.26)	24(52.17)
发病年龄[M(P₂₅，P₇₅)，岁]	33.00(21.00，53.00)	36.00(19.50，49.25)	- 0.446	0.656
病程≥ 3个月[例(%)]	18(78.26)	38(82.61)	0.012*	0.913
肌无力症状[例(%)]	20(86.96)	34(73.91)	0.338	0.561
全身症状[例(%)]	16(69.57)	21(45.65)	3.526	0.060
ANA检测	12	18
ANA阳性[例(%)]	8(8/12)	11(11/18)	—	1.000
血清CK[M(P₂₅，P₇₅)，U/L]	3599.00(2339.50，4901.75)	1660.00(703.00，5029.25)	- 1.927	0.054
合并其他肌炎抗体[例(%)]	7(30.43)	11(23.91)	0.338	0.561

Figure 1 Bilateral thigh muscle MRI findings Axial T₁WI showed diffuse mild adiposity of thigh muscle in patients with positive anti - Ku antibody (Panel 1a). Axial fat suppression T₂-FLAIR showed mild edema of the anterior and posterior thigh muscles in patient with positive anti-Ku antibody (Panel 1b). Axial T₁WI showed mild adiposity of thigh posterior muscle in patient with positive anti-PM-Scl-100 antibody (Panel 1c). Axial fat suppression T₂-FLAIR showed moderate to severe edema in the anterior and posterior thigh muscles and some medial muscles in patient with positive anti-PM-Scl-100 antibody (Panel 1d).

Table 2. HE staining results of skeletal muscle tissue biopsy [n = 70, case (%)]

观察指标	无	少数	部分	许多
肌内衣增生	58(82.86)	0(0.00)	12(17.14)	0(0.00)
肌束衣水肿	53(75.71)	0(0.00)	17(24.29)	0(0.00)
肌束衣炎性细胞浸润	36(51.43)	0(0.00)	34(48.57)	0(0.00)
肌束衣结缔组织增生	49(70.00)	10(14.29)	6(8.57)	5(7.14)
肌纤维肥大	54(77.14)	8(11.43)	8(11.43)	0(0.00)
肌纤维萎缩	6(8.57)	40(57.14)	16(22.86)	8(11.43)
肌纤维坏死	22(31.43)	36(51.43)	7(10.00)	5(7.14)
肌纤维再生	10(14.29)	42(60.00)	12(17.14)	6(8.57)

Table 3. Immunohistochemical staining results of skeletal muscle tissue biopsy [n = 67, case (%)]

观察指标	正常	少数	部分	许多
CD3⁺T淋巴细胞浸润	39(58.21)	20(29.85)	6(8.96)	2(2.99)
CD4⁺T淋巴细胞浸润	34(50.75)	21(31.34)	8(11.94)	4(5.97)
CD8⁺T淋巴细胞浸润	31(46.27)	33(49.25)	2(2.99)	1(1.49)
CD20⁺B淋巴细胞浸润	47(70.15)	13(19.40)	4(5.97)	3(4.48)
CD68⁺巨噬细胞浸润	8(11.94)	33(49.25)	12(17.91)	14(20.90)

Figure 2 Histopathological findings of skeletal muscle in patients with sclerosing myositis with positive anti- Ku antibody under light microscopy Muscle fiber necrosis and regeneration (Panel 2a). HE staining High power magnified Diffuse positive expression of MHC Ⅰ in the sarcolemma (Panel 2b). Immunohistochemical staining (EnVision) Median power magnified C5b9 deposition in some non-necrotic sarcolemma (Panel 2c). Immunohistochemical staining (EnVision) High power magnified CD3⁺ T lymphocytes, CD20⁺ B lymphocytes, and CD68⁺ macrophages infiltration in the perimysium and endomysium (Panel 2d-2f). Immunohistochemical staining (EnVision) Median power magnified

Figure 3 Histopathological findings of skeletal muscle in patients with sclerosing myositis with positive anti-PM-Scl antibody under light microscopy Muscle fiber necrosis, regeneration and inflammatory cells infiltration (Panel 3a). HE staining High power magnified Diffuse positive expression of MHC Ⅰ in the sarcolemma (Panel 3b). Immunohistochemical staining (EnVision) Median power magnified C5b9 deposition in the endomysia capillaries and non - necrotic sarcolemma (Panel 3c). Immunohistochemical staining (EnVision) High power magnified Some CD3⁺ T lymphocytes, few CD20⁺ B lymphocytes, and a large number of CD68⁺ macrophages infiltration in the perimysium, nearing blood vessels, and endomysium (Panel 3d-3f). Immunohistochemical staining (EnVision) Median power magnified

Table 4. Comparison of skeletal muscle histopathology data between anti-Ku antibody positive group and anti-PM- Scl antibody positive group [case (%)]

观察指标	抗Ku抗体阳性组(n = 23)	抗PM-Scl抗体阳性组(n = 46)	统计量值	P值
HE染色	23	44
肌内衣增生	6(26.09)	6(13.04)	1.021*	0.312
肌束衣水肿	7(30.43)	10(21.74)	0.624	0.429
肌束衣炎性细胞浸润	14(60.87)	20(43.48)	1.855	0.173
肌束衣结缔组织增生	7(30.43)	14(30.43)	0.000	1.000
肌纤维萎缩	22(95.65)	41(89.13)	—	0.656
肌纤维肥大	3(13.04)	13(28.26)	1.994	0.158
肌纤维坏死	18(78.26)	30(65.22)	1.232	0.267
肌纤维再生	20(86.96)	40(86.96)	0.000*	1.000
免疫组化染色	23	44
CD3⁺T淋巴细胞浸润	12(52.17)	16(36.36)	1.552	0.213
CD4⁺T淋巴细胞浸润	14(60.87)	18(40.91)	2.412	0.120
CD8⁺T淋巴细胞浸润	14(60.87)	22(50.00)	0.718	0.397
CD20⁺B淋巴细胞浸润	7(30.43)	13(29.55)	0.006	0.940
CD68⁺巨噬细胞浸润	22(95.65)	36(81.82)	2.486*	0.115
C5b9沉积	20(86.96)	27(61.36)	4.725	0.030
MHCⅠ阳性	22(95.65)	38(86.36)	—	0.408

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