アルミ入りワクチンからの血管炎発症の機序は解明されているのでは？
アルミ→NETs→ヒストン→血管炎
こんな研究結果が出ていました。
リコちゃんご推薦の新型インフルエンザワクチン接種の翌年に、インフルエンザワクチンを接種すると
28日以内の自然流産率が7.7倍増加するということのようです。
https://www.sciencedirect.com/science/article/pii/S0264410X17308666
Vaccine. 2017 Sep 25;35(40):5314-5322. doi: 10.1016/j.vaccine.2017.06.069.
- PMID:28917295
Abstract
Introduction
Inactivated influenza vaccine is recommended in any stage of pregnancy, but evidence of safety in early pregnancy is limited, including for vaccines containing A/H1N1pdm2009 (pH1N1) antigen. We sought to determine if receipt of vaccine containing pH1N1 was associated with spontaneous abortion (SAB).
Methods
We conducted a case-control study over two influenza seasons (2010–11, 2011–12) in the Vaccine Safety Datalink. Cases had SAB and controls had live births or stillbirths and were matched on site, date of last menstrual period, and age. Of 919 potential cases identified using diagnosis codes, 485 were eligible and confirmed by medical record review. Exposure was defined as vaccination with inactivated influenza vaccine before the SAB date; the primary exposure window was the 1–28 days before the SAB.
Results
The overall adjusted odds ratio (aOR) was 2.0 (95% CI, 1.1–3.6) for vaccine receipt in the 28-day exposure window; there was no association in other exposure windows. In season-specific analyses, the aOR in the 1–28 days was 3.7 (95% CI 1.4–9.4) in 2010–11 and 1.4 (95% CI 0.6–3.3) in 2011–12. The association was modified by influenza vaccination in the prior season (post hoc analysis). Among women who received pH1N1-containing vaccine in the previous influenza season, the aOR in the 1–28 days was 7.7 (95% CI 2.2–27.3); the aOR was 1.3 (95% CI 0.7–2.7) among women not vaccinated in the previous season. This effect modification was observed in each season.
Conclusion
SAB was associated with influenza vaccination in the preceding 28 days. The association was significant only among women vaccinated in the previous influenza season with pH1N1-containing vaccine. This study does not and cannot establish a causal relationship between repeated influenza vaccination and SAB, but further research is warranted.
https://www.cdc.gov/vaccines/schedules/vacc-updates/heplisav-b.html
18歳以上に適用になる新しいB型肝炎ワクチン、TLR９に結合する新しいアジュバント入りだそうです。
HepB-CpG contains yeast-derived recombinant HepB surface antigen (HBsAg) and is prepared by combining purified HBsAg with small synthetic immunostimulatory cytidine-phosphate-guanosine oligodeoxynucleotide (CpG-ODN) motifs (1018 adjuvant). The 1018 adjuvant binds to Toll-like receptor 9 to stimulate a directed immune response to HBsAg (1).
TLR9って教科書には細胞膜上ではなく、細胞の中にあるって書いてあるのですが、どうやって刺激するのか不思議です。
FDAで過去に2回蹴られて、3回目の正直で承認されたワクチンという噂です。
Heplisav-B (HepB-CpG)の名前で出ています。
酵母使って作っていますので、アレルギーの方は要注意です。
以下は、BMC Neuroscience201213:45 にある NF-κB p50ノックアウトマウスについての記載です。
「B細胞応答の欠陥、感染症への応答の欠陥、非特異的および特異的抗体産生の欠陥を示す」とありますが、
皆さんが口をそろえて仰る「自己抗体ができやすい特殊なマウス」でしょうか？
https://bmcneurosci.biomedcentral.com/articles/10.1186/1471-2202-13-45
Animals
Two month-old NF-κB p50 male knockout mice (B6;129P2-Nfkb1tm1Bal/J) (p50 −/−) and the recommended male controls (B6129PF2/J) (p50 +/+) were purchased from Jackson Laboratory (Bar Harbor, ME, USA). Targeted disruption of the NF-κB p50 subunit has been described in detail previously [24]. The p50−/− mice were homozygous for the deletion of the NF-κB p50 subunit, rendering them incapable of producing the p50 protein. Mice homozygous for the Nfkb1tm1Bal targeted mutation are viable and fertile. Homozygous mutant mice exhibit defective B cell responses, defective responses to infection, and also defects in basal and specific antibody production. Mice were maintained on a 12 hour light/12 hour dark cycle at room temperature (22°C) in the pathogen-free animal facility at the St. Boniface Research Centre. Mice were tested at 4 months of age. The University of Manitoba Animal Care and Use Committee approved all procedures, which conformed to the Guide to the Care and Use of Experimental Animals, published by the Canadian Council for Animal Care.
更に付け足すと、IgA→IgGクラススイッチに使われるAIDの産生に、NF-κBは必要ではありませんか？
メルクは2017年6月にサイバー攻撃にあって、ガーダシル９の製造に影響が出たと聞いたけれど、
それで、CDCに上納していたガーダシル９を借りたけれど、それでも不足していて
香港まで接種しに来ている中国人が怒って店員に噛みついたとかいう話は嘘だったのか？
この上納したガーダシル９は日本にも入っているのだろうか？
http://n.neurology.org/content/90/15_Supplement/P4.188
この男性の症状が、子宮頸がんワクチンの副反応の思春期女性の症状と被っている
週毎に認知力が変化する、計算ができない、語彙が少なくなる、不随意運動、記憶障害、歩けなくなる、
53歳の時に、認知障害と重度のアトピーが同時に発症
Objective: We seek to characterize the clinical symptoms and describe the treatment paradigm of a rare case of autoimmune encephalitis secondary to neuronal ganglionic acetylcholine receptor autoimmunity.
Background: Autoimmune encephalopathy can be used to describe a range of neuropsychiatric disorders in which autoantibodies are directed against central nervous system targets. While nicotinic ganglionic acetylcholine receptor autoimmunity has been commonly reported in dysautonomia and peripheral neuropathy, this type of autoimmunity has rarely been shown to cause encephalopathy. Currently, there is limited data regarding the cognitive and behavioral changes which occur in this syndrome, and the efficacy of immunomodulatory therapy.
Design/Methods: A case report.
Results: A 54 year-old previously healthy, right-handed male presented to clinic for evaluation of one year of cognitive impairment which was simultaneous with the onset of severe eczema. He reported weekly cognitive fluctuations and brief involuntary jerks. Symptoms involved difficulty with executive function, working memory, word finding, and calculations; there were no symptoms suggestive of dysautonomia. Cognitive exam revealed poor orientation, impaired comprehension and repetition, dysfunction of working memory and response inhibition, phonemic errors, paucity of functional words, ideomotor apraxia, acalculia, apraxic agraphia, and right-left confusion. Serologies indicated a high antibody titer to alpha-3 neuronal ganglionic acetylcholine receptor antibodies. MRI showed nonspecific T2 lesions. During IVIG treatment, jerking movements ceased and symptoms rapidly improved, particularly in language and short-term memory. His EEG, which was consistent with metabolic encephalopathy pretreatment, normalized after his IVIG course.
Conclusions: Encephalopathy associated with neuronal ganglionic acetylcholine receptor antibodies has been rarely reported, and tends to occur with dysautonomia and peripheral neuropathy. In this case, we describe the spectrum of cognitive findings our patient presented with along with his clinical and electrographic improvement following treatment with IVIG.
http://www.medalerts.org/vaersdb/findfield.php?IDNUMBER=726856
17歳 女性
サーバリックス接種の30日後発症、
自己免疫性脳炎、脳灌流圧低下、運動障害、疼痛、自律神経失調、歩行不能、性格変化。
Single-photon emission computed tomography (SPECT): Decreased blood flow. Intradermal nerve density: 21.3. Ganglionic AChR antibody: Alpha 3, positive; beta 4, positive. Antiganglioside antibody: IgM GM1, positive two plus. Spinal fluid GluR: Not performed. Other antibody: PR3-ANCA, positive. DPB1*0501: Positive.
http://www.medalerts.org/vaersdb/findfield.php?IDNUMBER=726846
19歳 女性
サーバリックス接種の30日後発症
自己免疫性脳炎、てんかん発作、脳灌流圧低下、疼痛、不適切な笑い
Single-photon emission computer tomography (SPECT): Decreased blood flow, Intradermal nerve density: Not performed, Ganglionic AChR antibody: Alpha 3, positive; beta 4, negative, Antiganglioside antibody: Negative, Spinal fluid GluR: Not performed, Other antibody: Not performed, DPB1 0501: Positive
http://www.medalerts.org/vaersdb/findfield.php?IDNUMBER=727260
15歳少女
サーバリックス接種の91日後発症
自己免疫性脳炎、脳灌流圧低下、疼痛、自律神経失調、記憶障害、倦怠、
Single-photon emission computed tomography (SPECT): Decreased blood flow; Intradermal nerve density: 4.8; Ganglionic AChR antibody: Alpha 3, negative; beta 4, positive; Antiganglioside antibody: Negative; Spinal fluid GluR: Not performed; Other antibody: Not performed; DPB1*0501: Positive
http://www.medalerts.org/vaersdb/findfield.php?IDNUMBER=727255
16歳 女性
接種の183日後発症、
脳灌流圧低下、疼痛、自律神経失調
Single-photon emission computed tomography (SPECT): Decreased blood flow; Intradermal nerve density: 13.5; Ganglionic AChR antibody: Alpha 3, positive; beta 4, negative; Antiganglioside antibody: Negative; Spinal fluid GluR: Not performed; Other antibody: Not performed; DPB1*0501: Positive.
http://www.medalerts.org/vaersdb/findfield.php?IDNUMBER=727304
16歳女性、サーバリックス接種の2年後、自己免疫性脳炎発症
脳灌流圧低下、運動異常、疼痛、不随意運動。
Single-photon emission computed tomography (SPECT): In 123 I-IMP SPECT, decreased blood flow was noted with laterality in its distribution and in multiple regions including cerebral cortex and basal nucleus. Intradermal nerve density: 9.5; Ganglionic AChR antibody: Alpha 3, positive; beta 4, negative; Antiganglioside antibody: IgM GM3, positive; Spinal fluid GluR: Positive; Other antibody: Not performed; DPB1*0501: Negative.
Paraneoplastic Limbic Encephalitis - Exposed
http://www.medalerts.org/vaersdb/findfield.php?IDNUMBER=730359
11歳 男性
2016年10月20日 ガーダシル９接種
テネシー州
抗NMDA受容体抗体陽性脳炎。
発病前に、頭痛、ウイルス感染様症状。
その後、様々な神経症状。易興奮、精神障害、攻撃的、発作、異様な作動（主に、唇と口）、制御不可能な脚の運動、頻脈（160-180）、自律神経障害。
入院中、緊張症、認知障害、記憶欠損、発話障害（失語、無言）。
| Vaccinated: | 2016-10-20 |
| Onset: | 2016-12-12 |
| Days after vaccination: | 53 |
| Submitted: | 0000-00-00 |
| Entered: | 2017-12-12 |
| Vaccination / Manufacturer | Lot / Dose | Site / Route |
| HPV9: HPV (GARDASIL 9) / MERCK & CO. INC. | M023169 / 2 | LA / IM |
Write-up: Anti-NMDA receptor encephalitis, also known as NMDA receptor antibody encephalitis, is an acute form of brain inflammation. It is caused by an immune system attack, primarily targeting the NR1 subunit of the NMDA receptor (N-methyl D-aspartate receptor). Experienced headaches, virus like symptoms for weeks prior to disease onset. Then presented with a variety of neurologic symptoms. These symptoms include agitation, psychosis, violent behavior, seizures, bizarre movements (mostly of the lips and mouth), uncontrollable motions to the legs, tachycardia (heart rate 160-180), and dysautonomia. While hospitalized, experienced catatonic state, impaired cognition, memory deficits, and speech problems (including aphasia and mutism). Required intensive inpatient rehabilitation (OT, PT, AND SPEECH). Medications: IVIG (Immunoglobulin therapy), RITUXIMAB, PREDNISONE, CHOLECALCIFEROL, LACOSAMIDE, LORAZEPAM, MELATONIN, OMEPRAZOLE, TRIMETHOPRIM-SULFAMETHOXAZOLE. HOSPITALIZATION: Hospital ? January 27 ? March 14, another Hospital Comprehensive Inpatient Rehabilitation ? March 14 ? March 28, Hospital Outpatient Day Program ? March 29 ? April 14.
http://www.medalerts.org/vaersdb/findfield.php?IDNUMBER=341216
13歳 女性 コロラド州
ガーダシル2回目接種後の1ヵ月後
抗NMDA受容体抗体が陽性であった脳炎
発症の5日前から、攻撃的になる
2ヵ月入院 医師から再発の可能性があると言われてた
| Vaccinated: | 2008-08-08 |
| Onset: | 2008-09-01 |
| Days after vaccination: | 24 |
| Submitted: | 2009-03-05 |
| Days after onset: | 185 |
| Entered: | 2009-03-06 |
| Days after submission: | 1 |
| Vaccination / Manufacturer | Lot / Dose | Site / Route |
| HPV4: HPV (GARDASIL) / MERCK & CO. INC. | 0927U / 2 | UN / UN |
Diagnostic Lab Data: Unknown LABS: EEG abnormal. MRI WNL. Repeat LP done 10/3: wbc 42(H), protein & glucose (N), c/s neg. Initial CSF: WBC 142(H), RBC 5, neutros 2, lymphs 92, monos 6, glucose 54, protein 34, c/s neg. CBC: WBC 6900, neutros 62, bands 1, lymphs 27, monos 10. CMP. Urine drug screen neg. CRP & ESR WNL. EBV IgM 1.161(H)
Write-up: Information has been received from a physician concerning a female patient who in July or August of 2008, was vaccinated with her second dose of GARDASIL. In September 2008, the patient had NMDA antibody receptor and encephalitis. Drug treatment was required. The patient presented at the emergency room and was hospitalized for 2 months. At the time of reporting the patient was recovering from the NMDA antibody receptor encephalitis. The patient was told that she could have recurring episodes. It was unknown if there would be significant disability. Additional information has been requested. 4/24/09 Received hospital medical records of 9/29-11/25/2008. FINAL DX: NMDA receptor positive encephalopathy; delerium; g-tube placement; left brachiocephalic IVC clot associated w/PICC line placement; antiphospholipid antibodies. Records reveal patient symptoms noted in outlying ER in addition to aggression began approx 5 days prior. Course waxed & waned w/intermittent decreased alertness & delerium, decreased O2 sats & was in/out of PICU. Tx w/IVIG x 5 days, steroids, IV antibiotics/antivirals, plasmaphersis x 4 days, antineoplastics, feeding tube placement & anticoagulants. Neuro, Rheum & Psych consult done. Slowly improved & d/c to home w/PCP, Thrombophilia, Rheum, REhab & surgery clinic appts. 4/7/09 Received hospital medical records of 9/27-9/29/2008. FINAL DX: probable encephalitis Records reveal patient experienced acute confusion, mental status change, repetitive garbled speech then aphasia, excitable. In hospital had alternating periods of quiescence & agitation, speech garbled, perseverating, neologisms & frequently aphasic. ID & Neuro consults done. Transferred to higher level of care.
2018年2月に、日本でのサーバリックス後の自己免疫性脳炎が8件VAERSに報告されています。
HPVワクチン接種後の女性における抗NMDA受容体脳炎の発症について、製薬会社を介して医師から報告された。
また、同じく日本から、ガーダシル後の自己免疫性脳炎が2015年に報告されています。
http://www.medalerts.org/vaersdb/findfield.php?IDNUMBER=582474