Folli F, Solimena M, Cofiell R, Austoni M, Tallini G, Fassetta G, Bates D, Cartlidge N, Bottazzo G F, Piccolo G, De Camilli P
Department of Cell Biology, Yale University School of Medicine, New Haven, Conn.
N Engl J Med. 1993 Feb 25;328(8):546-51. doi: 10.1056/NEJM199302253280805.
The stiff-man syndrome is a rare disease of the central nervous system characterized by progressive rigidity of the body musculature. Autoantibodies directed against glutamic acid decarboxylase are present in about 60 percent of patients with the syndrome. In this group, there is a striking association of the stiff-man syndrome with organ-specific autoimmune diseases, primarily insulin-dependent diabetes mellitus.
We studied three women with the stiff-man syndrome and breast cancer, seeking autoantibodies directed against nervous system antigens in serum and cerebrospinal fluid by immunocytochemical techniques, Western blotting, and immunoprecipitation.
Autoantibodies directed against a 128-kd brain protein were found in two of the women with the stiff-man syndrome and breast cancer. These results led to a search for breast cancer in the third patient with the stiff-man syndrome, who also had autoantibodies. A small invasive ductal carcinoma was detected by ultrasonography and removed. Serum samples from all three patients were negative for autoantibodies directed against glutamic acid decarboxylase. Autoantibodies against the 128-kd antigen were not detected in control patients with the stiff-man syndrome without breast cancer or in patients with cancer who did not have the syndrome. Within the nervous system, the 128-kd autoantigen was localized in neurons and concentrated at synapses.
In a subgroup of patients with the stiff-man syndrome, the condition is likely to have an autoimmune paraneoplastic origin. The detection of autoantibodies against the 128-kd antigen in patients with this syndrome should be considered an indication to search for an occult breast cancer.
僵人综合征是一种罕见的中枢神经系统疾病，其特征为身体肌肉组织进行性僵硬。约60%的该综合征患者体内存在针对谷氨酸脱羧酶的自身抗体。在这组患者中，僵人综合征与器官特异性自身免疫性疾病，主要是胰岛素依赖型糖尿病，存在显著关联。
我们研究了三名患有僵人综合征和乳腺癌的女性，通过免疫细胞化学技术、蛋白质印迹法和免疫沉淀法在血清和脑脊液中寻找针对神经系统抗原的自身抗体。
在两名患有僵人综合征和乳腺癌的女性中发现了针对一种128kd脑蛋白的自身抗体。这些结果促使对第三名患有僵人综合征且也有自身抗体的患者进行乳腺癌筛查。通过超声检查发现了一个小的浸润性导管癌并将其切除。所有三名患者的血清样本中针对谷氨酸脱羧酶的自身抗体均为阴性。在没有乳腺癌的僵人综合征对照患者或没有该综合征的癌症患者中未检测到针对128kd抗原的自身抗体。在神经系统内，128kd自身抗原定位于神经元并集中在突触处。
在僵人综合征患者的一个亚组中，该病可能有自身免疫性副肿瘤起源。在患有该综合征的患者中检测到针对128kd抗原的自身抗体应被视为寻找隐匿性乳腺癌的指征。
