Autoantibodies in post-treatment Lyme disease and association with clinical symptoms.

OBJECTIVES: Autoantibodies have been described in the post-infectious state, specifically after Lyme disease and COVID-19. We aimed to describe the prevalence and potential clinical utility of several commercially available autoantibodies after these infections. METHODS: Euroimmun panels (myositis, scleroderma and ANA5) were assayed using sera from patients with Lyme disease with return to health (RTH) (n=70), post-treatment Lyme disease (n=58), COVID-19 RTH (n=47) and post-acute symptoms of COVID-19 (n=22). The post-Lyme questionnaire of symptoms (PLQS) was used to determine symptom burden after Lyme disease. RESULTS: There was no statistically significant difference in autoantibody prevalence across the four groups (p=0.746). A total of 21 different antibodies were found in the Lyme cohorts and 8 different antibodies in the COVID-19 cohorts. The prevalence of scleroderma-associated antibodies was higher after Lyme disease than COVID-19 (12.5% vs. 2.9%, p=0.026). There was no statistically significant difference in symptom burden based on antibody status. CONCLUSIONS: Several autoantibodies were found after Borrelia burgdorferi and SARS-CoV2 infection, although the prevalence was similar in those with persistent symptoms and those who returned to health. While our data show no difference in autoantibody prevalence across the four post-infectious states, we do not imply that autoantibodies are irrelevant in this setting. Rather, this study highlights the need for novel antibody discovery in larger cohorts of well-defined patient populations.

Confirming Parkinson Disease Diagnosis: Patterns of Diagnostic Changes by Movement Disorder Specialists.

Background: The American Academy of Neurology Parkinson Disease (PD) quality measures include an annual diagnostic review. Objective: To investigate the frequency and pattern of changes in diagnoses between PD and other causes of parkinsonism. Methods: This prospective longitudinal cohort study included consented patients diagnosed with PD at least once and a minimum of two times at the Movement Disorders Center between 2002 and 2017. Movement disorder specialists confirmed and documented diagnoses at every visit. Longitudinal changes in diagnoses were identified across visits. Results: Of 1567 patients with parkinsonism, 174 had non-PD parkinsonism with no change over time. Of 1393 patients diagnosed with PD at least once, 94% (N = 1308) had no change of diagnosis over time and 6% (N = 85) had a change of diagnosis including PD ⟷ drug-induced parkinsonism (DIP) (27.1%), PD ⟷ multiple system atrophy (MSA) (20.0%), PD ⟷ progressive supranuclear palsy (PSP) (18.8%), PD ⟷ Lewy body dementia (DLB) (16.5%), PD⟷ vascular parkinsonism (9.4%), more than two diagnoses (4.7%), and PD ⟷ corticobasal syndrome (CBS) (3.5%). The direction of diagnostic switches was as follows: PD ⟶ other parkinsonism diseases (36.5%), other parkinsonism diseases ⟶ PD (31.8%), and 31.8% of multiple switches. There were no significant differences in duration of follow-up, age at first visit, gender, race, marital status, education, income, cognition, or employment between the stable and unstable groups. Diagnostic change was associated with greater PD severity and greater medical comorbidity. Conclusion: Over a 15-year period, movement disorder specialists changed their clinical diagnosis of PD in 6% of patients. The most common diagnostic switches, to or from PD, were DIP, MSA, PSP, and DLB. This study describes routine clinical diagnostic patterns in the absence of pathologic confirmation. The presence of diverse diagnostic changes over time underscores the value of confirming PD diagnosis.

Macrophage activation syndrome in MDA5 antibody-positive dermatomyositis and COVID-19 infection.

BACKGROUND: Macrophage activation syndrome (MAS) is a rare multiorgan system disorder that may present as a fatal complication of underlying rheumatological disease, including dermatomyositis. CASE PRESENTATION: Here, we report the case of a 65-year-old Caucasian female with a history of psoriasis and a recent diagnosis of Coronavirus disease 2019 (COVID-19) who presented with progressive generalized weakness, joint pains, an erythematous rash, shortness of breath, and weight loss. She was ultimately diagnosed with biopsy-confirmed melanoma differentiation-associated protein 5 (MDA5)-positive dermatomyositis complicated by MAS, requiring intravenous immunoglobulin and high-dose methylprednisolone. CONCLUSIONS: This report serves as a clinical reminder of the rare, yet clinically relevant association between MDA5-positive dermatomyositis and MAS, as well as highlights the potential contribution of other immune system activating diseases, such as COVID-19, associated with a cytokine storm and hyperinflammatory state.

Effect of influenza vaccine on tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in older adults.

Influenza immunization is recommended for older adults annually, and has been reported to have cardiovascular protective effects. TNF-related weak inducer of apoptosis (TWEAK), an inflammatory mediator implicated in the development of cardiovascular diseases, could be a mechanism for such effect. The objective of this study was to evaluate the effect of influenza vaccine on TWEAK levels. Older persons over 70 years of age were recruited during 2007-2008 influenza season and immunized with the standard dose trivalent inactivated influenza vaccine. Frailty was evaluated using a validated set of criteria. Sera were collected immediately before and during the 4th week after vaccination. Pre- and post-vaccination levels of TWEAK, soluble CD163 (sCD163) and strain-specific influenza antibody titers were measured in 69 participants. Multiple regression analyses were employed to examine the effect of influenza vaccine on TWEAK and sCD163, adjusting for age, sex, and hypertension. Post-vaccination TWEAK [mean ±â€¯standard deviation (SD) = 591.7 ±â€¯290.1 pg/ml] was significantly lower than pre-vaccination level (690.6 ±â€¯330.0 pg/ml) (p = .003). No significant difference was observed between pre and post-vaccination sCD163 levels (p = .71). Post-vaccination TWEAK levels were significantly higher in men (p = .01) and in participants with college or higher level of education (p = .044). There was no significant difference in post-vaccination TWEAK according to other demographics or pre-existing medical conditions. A 2-fold or greater antibody titer against H1N1 vaccine strain was associated with a more pronounced reduction in TWEAK at the p < .10 level (p = .091). A time by frailty interaction term (p = .091) indicated that the vaccination-induced reduction of TWEAK was greatest among frail individuals. These results of this observational study indicate that the impact of Influenza vaccine on TWEAK, including the role of specific antibody responses of specific vaccine strains and frailty status, warrants further investigation. Such investigation may elucidate whether this effect plays a role in mediating cardiovascular protection of influenza vaccination.