A Comprehensive Clinical, Microbiological and Immunological Assessment of Patients With Suspected Post Treatment Lyme Disease Syndrome and Selected Control Populations

* INCLUSION CRITERIA: SCREENING FOR SUSPECTED PTLDS Age \>= 13 years old, suspect of suffering from Lyme disease POST-TREATMENT LYME DISEASE SYNDROME (PTLDS) For the purposes of this study, PTLDS is defined as (1) occurring in male or female patients aged 13 and above (2) who have been diagnosed with confirmed or probable Lyme disease per CDC definition (https://wwwn.cdc.gov/nndss/conditions/lyme-disease/case-definition/2017/). Study physician will review history to confirm probable cases. (3) They have received recommended antibiotic therapy (4) and have persistent or relapsing symptoms and/or signs for at least six months after therapy \[4, 5\]. (5) They also should have no other documented explanation for their signs and symptoms. LYME ARTHRITIS CONTROLS For the purposes of this study, Lyme arthritis is defined as occurring in an otherwise healthy male or female aged 18 and above who have intermittent episodes of arthritis involving one or few joints, without any other cause being documented, and have positive serum antibodies to B. burgdorferi confirmed by IgG Western blot according to the CDC criteria. RECOVERED CONTROLS For the purposes of this study, a recovered control is defined as an otherwise healthy male or female aged 18 and above who has had confirmed or probable Lyme disease, fulfilling the CDC Lyme Disease National Surveillance Case Definition (appendix 5), and who had received accepted antibiotic treatment for Lyme disease \[5\] (at least 3 months since the end of antibiotic therapy before protocol evaluation) and who are currently asymptomatic. SEROPOSITIVE CONTROLS For the purposes of this study, a seropositive control is defined as an otherwise healthy male or female aged 18 and above who has positive serum IgG antibody response to B. burgdorferi by Western blot according to the CDC criteria and are asymptomatic and who recall no episodes of disease compatible with Lyme infection and have not received antibiotic therapy for Lyme disease. OSPA VACCINATED CONTROL For the purposes of this study, an OspA vaccinated control is defined as an otherwise healthy male or female age 18 and above who has received at least two doses of the OspA vaccine for Lyme disease (Lymerix ). These controls may have a positive ELISA for B. burgdorferi but a negative (or unreadable) IgG western blot. MULTIPLE SCLEROSIS CONTROLS For the purposes of this study, a multiple sclerosis control is defined as an otherwise healthy male or female aged 18 and above with relapsing-remitting or progressive multiple sclerosis as defined by the Clinical Trial Committee of the National Multiple Sclerosis Society and no evidence of prior exposure to B. burgdorferi as indicate by negative history for Lyme disease and negative western blot for B. burgdorferi in the serum by the CDC criteria. Patients should have a Kurtzke or Expanded Disability Status Scale (EDSS) between 1 and 5. HEALTHY VOLUNTEERS For the purpose of this study, a healthy volunteer is defined as healthy male or female, age 18 and above, with no history compatible with Lyme disease and negative serological testing to B. burgdorferi by the CDC criteria. GENERAL EXCLUSION CRITERIA 1. Age less than 18 (less than 13 for patients with PTLDS) 2. Weight less than 70 Lb. (35 kg) 3. Pregnancy or lactation 4. Women with childbearing potential who are sexually active with a male partner and unwilling to use effective contraception during the evaluation and treatment phases of the protocol. 5. Clinically significant laboratory abnormalities including positive test for syphilis (RPR), HBsAg, anti-HCV, anti-HIV. 6. Chronic medication use will be evaluated in a case-by-case basis. 7. Not able to understand all of the requirements of the study or unable to give informed consent and/or comply with all aspects of the evaluation. 8. All study participants must agree to allow their samples to be used for future research. EXCLUSION CRITERIA FOR PTLDS PATIENTS AND LYME ARTHRITIS CONTROLS: In addition to the general exclusion criteria, these individuals will be excluded for: 1. Use of immunosuppressive drugs such as systemic (but not topical or inhalant) steroids and cytotoxic agents. 2. History of any recognized autoimmune disease such as rheumatoid arthritis, vasculitis, systemic erythematous lupus, etc. 3. Serious pre-existing or concurrent chronic medical or psychiatric illnesses other than Lyme disease. 4. Past history of significant head trauma, alcohol or substance abuse in the past 5 years or other medical illness that might produce neurologic deficit (such as cerebrovascular disease). 5. Use of systemic antibiotics in the previous month. 6. Use of immunomodulators such as interferons. 7. Chronic medication use will be evaluated in a case-by-case basis 8. Patients will be excluded from this protocol if they are judged by the principal investigator as having a significant impairment in their capacity for judgment and reasoning that compromise their ability to make decisions in their best interest. EXCLUSION CRITERIA FOR RECOVERED, SEROPOSITIVE, OSPA VACCINATED AND HEALTHY VOLUNTEERS CONTROLS: In addition to the above applicable exclusion criteria (general exclusion criteria and exclusion criteria for PTLDS patients and Lyme arthritis controls), these individuals will be excluded for: 1\. Pre-existing or concurrent serious chronic medical or psychiatric illness. EXCLUSION CRITERIA FOR MULTIPLE SCLEROSIS CONTROLS: In addition to the above general exclusion criteria, these individuals will be excluded for: 1. Pre-existing or concurrent serious psychiatric or chronic medical illness besides Multiple Sclerosis. 2. Past history of significant head trauma, alcohol or substance abuse in the past 5 years or other medical illness, besides Multiple Sclerosis, that might produce neurologic deficit (such as cerebrovascular disease). 3. Previously received total lymphoid irradiation (TLI) or cladribine. 4. Has used immunoactive medications (exclud