Congenital myopathy-14 (CMYO14) is an ultrarare autosomal recessive disorder caused by biallelic variants in MYL1, with only four patients reported to date. We describe what is likely the fifth reported patient, a neonate with severe hypotonia, respiratory insufficiency, and skeletal anomalies showing distinct histological changes of skeletal muscle consistent with all previously described patients. The patient carried a novel homozygous intron variant (c.479-25T>C, p.(?)) in MYL1. RNA analysis of patient muscle demonstrated aberrant splicing, with inclusion of 19 bp from intron 4 in most transcripts, resulting in a frameshift and premature stop codon, and in-frame skipping of exons 4-5 in a minority of transcripts encompassing functional domains. In addition to core CMYO14 features, the patient presented with craniofacial anomalies not previously described. This case broadens the genotypic and phenotypic spectrum of MYL1-related disease and underscores the diagnostic importance of intron variants, highlighting the value of combining in silico splice prediction with functional RNA analyses.

Physical performance can be improved in aerobic athletes and breath-hold divers (BHD) by limb exposure to repetitive ischemia: remote ischemic conditioning (RIC). RIC protects against cardiac ischemia, and its blood-borne transferable substrate could be lactate. Accordingly, lactate added to whale blood increases oxygen unloading and adult seals possess higher cardiac lactate dehydrogenase activity (LDHa) than terrestrial mammals. Because BHD and adult diving mammals share adaptations to hypoxia, including lactate metabolization during apnea, we hypothesized that BHD compared to BMI/VO2max-matched aerobic controls have higher LDHa and lactate added to blood from BHD unloads oxygen more efficiently. Six BHD and six matched aerobic controls underwent RIC: three cycles of 5-min inflation and 4-min deflation of a blood pressure cuff on the dominant arm, maximum apnea after three submaximal apneas (BHD only), and a VO2max-test. Blood-samples were collected from the nondominant radial artery and the vena basilica of the dominant arm at rest, before termination of the three interventions, and for LDHa. Blood gases were compared to samples added lactate or placebo suspension. BHD had ⁓30% higher cardiac/erythrocyte LDHa compared to controls (p < 0.05). Lactate added to arterial blood from BHD after RIC increased oxygen unloading (p < 0.05). PaO2 decreased ⁓66% during apnea (375+/-49 s; p < 0.001; BHD only). We conclude that 1 (erythrocyte- and cardiac-LDHa is higher in BHD compared to matched controls, and 2) lactate facilitates oxygen-unloading in blood from BHD after RIC, similar to diving mammals.

Protein glycosylation defects can present with early-onset brain malformations and muscular dystrophy or milder, late-onset muscular dystrophy. Here, we report a new glycosylation defect with an atypical phenotype of late-onset, progressive, severe brain atrophy and muscular dystrophy in a 47-year-old man. Exome sequencing revealed a homozygous highly deleterious c.478G>T (p.G160W) variant in the B3GNT4 gene. A knock-in mouse model replicated the patient’s muscle histology. B3GNT4 is expressed at very low levels in the thalamus, and this region was selectively preserved in the patient. The study demonstrates the first disease associated with one of the seven B3GNT galactosyltransferases and the importance of B3GNT4 in adolescence to adult muscle and CNS development.

AIMS:The aim of the study was to investigate whether differences in paracetamol pharmacokinetics (PK) between spinal muscular atrophy (SMA) patients and healthy controls (HC) could be attributed to specific clinical covariates. METHODS:Nonlinear mixed-effects modelling (NONMEM 7.4) was used to develop a population PK model, explore covariates for paracetamol and its metabolites and perform simulations. RESULTS:With body weight as allometric scaling in the model, SMA disease resulted in a 58% (95% confidence interval [CI]: 20%-130%) increase in the volume of distribution for paracetamol and its metabolites compared to healthy controls. Decreased plasma myoglobin and plasma bilirubin concentrations, seen in SMA patients, resulted in a higher paracetamol leftover clearance (SMA, median: 13.30 L/h/70 kg, 95% CI: 9.14-18.29%; HC, median: 4.05 L/h/70 kg, 95% CI: 3.38-8.83%) and a shift from slower sulfate formation clearance (SMA, median: 8.78 L/h/70 kg, 95% CI: 7.22-9.61%; HC, median: 9.30 L/h/70 kg, 95% CI: 8.42-10.15%) and faster oxidative metabolites elimination clearance (SMA, median: 3.74 L/h/70 kg, 95% CI: 3.31-4.72%; HC, median: 3.25 L/h/70 kg, 95% CI: 2.87-3.92%). Simulations revealed that in SMA patients, higher bodyweight was associated with increased exposure to paracetamol and its metabolites. CONCLUSIONS:The differences in PK between SMA patients and healthy controls could be explained by body weight and the disease itself. SMA patients should be dosed cautiously, ensuring doses do not exceed the recommended body weight adjusted limit.

INTRODUCTION/AIMS:Primary hypokalemic periodic paralysis (HypoPP) can present with periodic paralysis and/or permanent muscle weakness. Permanent weakness is accompanied by fat replacement of the muscle. It is unknown whether the permanent muscle weakness is solely due to fat replacement or if other factors affect the ability of the remaining muscle fibers to contract. We aimed to investigate muscle fat replacement and contractility in persons with HypoPP-causing variants in CACNA1S and to compare the results to healthy controls. METHODS:In this cross-sectional study, we used T1-weighted and 2-point Dixon magnetic resonance imaging (MRI) to assess fat replacement of the muscle and stationary dynamometry to assess muscle strength. Contractility was determined by maximal muscle contraction divided by the contractile cross-sectional muscle area. RESULTS:We included 45 persons with HypoPP-causing variants in CACNA1S and data from 37 healthy controls. We found that fat fraction was increased in ankle dorsiflexors and knee extensors and flexors, and further found that muscle strength was decreased in knee extensors and flexors in persons with HypoPP-causing variants in CACNA1S compared to healthy controls. Additionally, we found decreased contractility of thigh muscles in persons with HypoPP-causing variants in CACNA1S compared to healthy controls. DISCUSSION:The decreased contractility could relate to skeletal muscle voltage-gated calcium channel dysfunction, subclinical attacks of paralysis, and/or changed muscle architecture, but this needs further investigation.

Limb-girdle muscular dystrophy Type 2A/R1 or calpain-3 deficiency is the most common autosomal recessive limb-girdle muscular dystrophy. However, in recent years, autosomal dominant cases and families with calpain-3 deficiency have been reported, and there is an emerging interest in looking for single variants in the calpain-3 gene in mildly to moderately affected patients with limb-girdle muscular dystrophy without biallelic gene variants in CAPN3. Here, we report four cases with creatine kinase levels above 1500 U/L, mild-to-moderate proximal weakness, waddling gait, and scapular winging. Two patients, a son and his father, are heterozygous for the CAPN3 variant c.304C>T; p.(Pro102Ser), which has previously been reported in patients with compound heterozygous variants in CAPN3. The third and fourth patients were heterozygous for c.1371C>G; p.(Asn457Lys) and c.1490C>T; p.Ala497_Glu508del, respectively, neither of which has been reported before. All four patients had a near-complete loss of calpain-3 as determined by western blotting. While inherited autosomal dominant calpainopathy has now been firmly established, additional single cases of dominant calpainopathy are likely to emerge; some will be associated with clinical findings from parents or siblings, while others will arise from spontaneous mutations, but nevertheless with similar clinical findings of mild-to-moderate proximal weakness, increased level of creatine kinase, and near-complete loss of calpain-3 protein in affected individuals. This report expands the known number of variants causing dominant calpainopathy from 8 to 11 that appears to exclusively reside in two out of four domains that make up calpain-3. This information could aid in determining whether a CAPN3 variant of unknown significance is pathological.

Multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare inborn metabolic myopathy affecting fat and protein metabolism. Patients with late-onset MADD typically present with exercise intolerance and muscle weakness. We present a patient with an acute, very late-onset symptom debut at 52 years of age. Over 5 months, the patient deteriorated from asymptomatic to almost complete loss of ambulation. He had a substantial weight loss, head-drop, progressive proximal limb and chewing weakness. Due to the rapid progression, amyotrophic lateral sclerosis, myositis, myasthenia gravis and a paraneoplastic syndrome in relation to underlying malignancy were considered first. A 2-[18F] FDG PET/CT scan was performed to exclude a paraneoplastic syndrome. The scan revealed diffuse and symmetric, pathologically high 2-[18F] FDG-uptake in the patient's neck, shoulder, and paravertebral muscles, which was later suggested as a sign of a metabolic myopathy. Muscle biopsy (Oil Red O staining) and acylcarnitine profile (elevated C5-C18 acylcarnitines) findings suggested MADD, which was confirmed by genetic analysis showing biallelic variants in the ETFDH gene (c.1763A>G, p.(His588Arg); c.897G>A, p.(Leu299=)). After 1 month of dietary intervention and daily diet supplements (riboflavin 400 mg TID, levocarnitine 1 g TID, Q10 150 mg qD in two doses), the patient had almost recovered to his habitual level. A posttreatment muscle biopsy showed less disrupted ultrastructure of the myofibers. We learned from this case of rapid and late-onset MADD that 2-[18F] FDG PET/CT, with diffuse and symmetric 2-[18F] FDG-uptake in skeletal muscle, can be valuable in clarifying this rare diagnosis.

[This corrects the article DOI: 10.1212/NXG.0000000000200211.].

IntroductionElite breath-hold divers (BHD) enduring apneas of more than 5 min are characterized by tolerance to arterial blood oxygen levels of 4.3 kPa and low oxygen-consumption in their hearts and skeletal muscles, similar to adult seals. Adult seals possess an adaptive higher hemoglobin-concentration and Bohr effect than pups, and when sedated, adult seals demonstrate a blood shift from the spleen towards the brain, lungs, and heart during apnea. We hypothesized these observations to be similar in human BHD. Therefore, we measured hemoglobin- and 2,3-biphosphoglycerate-concentrations in BHD (n = 11) and matched controls (n = 11) at rest, while myocardial mass, spleen and lower extremity volumes were assessed at rest and during apnea in BHD.Methods and resultsAfter 4 min of apnea, left ventricular myocardial mass (LVMM) determined by 15O-H2O-PET/CT (n = 6) and cardiac MRI (n = 6), was unaltered compared to rest. During maximum apnea (∼6 min), lower extremity volume assessed by DXA-scan revealed a ∼268 mL decrease, and spleen volume, assessed by ultrasonography, decreased ∼102 mL. Compared to age, BMI and VO2max matched controls (n = 11), BHD had similar spleen sizes and 2,3- biphosphoglycerate-concentrations, but higher total hemoglobin-concentrations.ConclusionOur results indicate: 1) Apnea training in BHD may increase hemoglobin concentration as an oxygen conserving adaptation similar to adult diving mammals. 2) The blood shift during dry apnea in BHD is 162% more from the lower extremities than from the spleen. 3) In contrast to the previous theory of the blood shift demonstrated in sedated adult seals, blood shift is not towards the heart during dry apnea in humans.

Introduction Elite breath-hold divers (BHD) possess several oxygen conserving adaptations to endure long dives similar to diving mammals. During dives, Bottlenose Dolphins may increase the alveolar ventilation (VA) to perfusion (Q) ratio to increase alveolar oxygen delivery. We hypothesized that BHD possess similar adaptive mechanisms during apnea.Methods and results Pulmonary blood volume (PBV) was determined by echocardiography, 15O-H2O PET/CT, and cardiac MRi, (n = 6) during and after maximum apneas. Pulmonary function was determined by body box spirometry and compared to matched controls. After 2 min of apnea, the PBV determined by echocardiography and 15O-H2O-PET/CT decreased by 26% and 41%, respectively. After 4 min of apnea, the PBV assessed by echocardiography and cardiac MRi decreased by 48% and 67%, respectively (n = 6). Fractional saturation (F)O2Hb determined by arterial blood-gas-analyses collected after warm-up and a 5-minute pool-apnea (n = 9) decreased by 43%. Compared to matched controls (n = 8), spirometry revealed a higher total and alveolar-lung-capacity in BHD (n = 9), but a lower diffusion-constant.Conclusion Our results contrast with previous studies, that demonstrated similar lung gas transfer in BHD and matched controls. We conclude that elite BHD 1) have a lower diffusion constant than matched controls, and 2) gradually decrease PBV during apnea and in turn increase VA/Q to increase alveolar oxygen delivery during maximum apnea. We suggest that BHD possess pulmonary adaptations similar to diving mammals to tolerate decreasing tissue oxygenation.New and noteworthy This manuscript addresses novel knowledge on tolerance to hypoxia during diving, which is shared by elite breath-hold divers and adult diving mammals: Our study indicates that elite breath-hold divers gradually decrease pulmonary blood volume and in turn increase VA/Q, to increase alveolar oxygen delivery during maximum apnea to tolerate decreasing oxygen levels similar to the Bottlenose Dolphin.

Proinflammatory cytokines, such as interleukin (IL)-8, IL6, and IL10, have been found to be higher in patients with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) compared to healthy controls. When comparing immunological pathway activation in patients with hereditary polyneuropathy (Charcot-Marie-Tooth (CMT)) and CIDP, similar levels of proinflammatory cytokines have been found. Furthermore, increased levels of components of the complement pathway in mouse models and CMT patients indicate inflammatory pathway activation in CMT. This suggests that inflammatory pathway activation is a driver for disease progression in CIDP as well as CMT, but larger studies are needed. The aim with our project is to investigate potential activation of immunologic pathways in a larger cohort of patients with CMT and CIDP. We include patients diagnosed with CIDP according to EAN/PNS diagnostic criteria and patients with genetically verified CMT followed at a specialized neuromuscular center. The study is a case-control study, with CIDP patients as disease controls. Patients are examined with evaluation of disease severity and blood biomarkers. Primary disease severity score is Inflammatory Neuropathy Cause and Treatment (INCAT), a validated outcome measure for disease severity in polyneuropathies. Secondary scores are 80-points Medical Research Council (MRC)-sum score, and handgrip strength, which are all validated outcome measures for disease severity in polyneuropathies. Plasma and serum will be collected according to protocol and frozen to -80 degrees Celsius, assuring stability of biomarkers when samples are frozen. The concentration of interleukins, TNF-alfa and complement factor will be analyzed using Multiplex assay in our laboratory. To test for differences in interleukin, TNF-alfa, and complement levels in CIDP patients compared to CMT patients, we will use two-sample t-test. Correlation between levels of interleukins and disease severity will be examined using Spearman correlation. A total of 144 patients have been included, 65 patients with CIDP and 79 patients with CMT. All patients have been examined with medical examination, physiotherapeutic tests, and blood samples and data are currently being analyzed. Blood samples are ready for analysis and results are expected in September 2024. Preliminary results will be presented at the conference. There is a vast need for understanding the variability of symptoms in polyneuropathies. Immunological activation may explain the clinical variability and could potentially lead to future “biomarker-guided” treatments.

Primary hypokalemic periodic paralysis (HypoPP) is a skeletal muscle channelopathy most commonly caused by pathogenic variants in the calcium channel gene, CACNA1S. HypoPP can present with attacks of paralysis and/or permanent muscle weakness. Previous studies have shown that patients with HypoPP can have impaired quality of life (QoL). In this cross-sectional study, we aimed to describe the QoL in patients with HypoPP caused by pathogenic variants in CACNA1S using The Individualized Neuromuscular Quality of Life (INQoL) questionnaire, a validated tool to measure the QoL of patients with neuromuscular diseases (higher score, worse QoL). We showed that muscle weakness and fatigue were the symptoms with the greatest impact on participants' lives and that “activities”, in the life domain of the INQoL, was most affected by HypoPP. Furthermore, we showed that the total INQoL score increased with age. Low QoL was primarily driven by progressive permanent muscle weakness and not attacks of paralysis, although half of the participants reported that attacks of paralysis challenged their daily life. The results suggest that special attention should be given to muscle weakness and fatigue in patients with HypoPP.

Acute liver failure has been reported sporadically in patients with spinal muscular atrophy (SMA) and other neuromuscular disorders with low skeletal muscle mass receiving recommended dosages of acetaminophen. It is suggested that low skeletal muscle mass may add to the risk of toxicity. We aimed to describe the pharmacokinetics and safety of acetaminophen in patients with SMA. We analyzed acetaminophen metabolites and liver biomarkers in plasma from SMA patients and healthy controls (HC) every hour for six or eight hours on day 1 and day 3 of treatment with therapeutic doses of acetaminophen. Twelve patients with SMA (six adults and six children) and 11 HC participated in the study. Adult patients with SMA had significantly lower clearance of acetaminophen compared to HC (14.1 L/h vs. 21.5 L/h). Formation clearance of acetaminophen metabolites, glucuronide, sulfate, and oxidative metabolites were two-fold lower in the patients compared to HC. The liver transaminases and microRNAs increased nine-fold in one adult SMA patient after two days of treatment. The other patients and HC did not develop abnormal liver biomarkers. In this study, patients with SMA had lower clearance and slower metabolism of acetaminophen, and one patient developed liver involvement. We recommend giving 15 mg/kg/dose to SMA adults (with a maximum of 40 0 0 mg/day) and monitoring standard liver biomarkers 48 h after first-time treatment of acetaminophen.0 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Background and Objectives:Primary hypokalemic periodic paralysis (HypoPP) is a muscle channelopathy that can cause periodic paralysis and permanent weakness. Currently, little is known about how progressive this myopathy is. Natural history data for HypoPP can potentially answer the question of progressiveness and form the basis for outcome measures to be used in follow-up and emerging treatment trials. We aimed to describe the natural history of HypoPP and assess whether quantitative fat imaging is a valuable biomarker to monitor disease progression. Methods:In this prospective follow-up study, we examined disease progression using Dixon MRI to monitor changes in fat replacement of the muscle and stationary dynamometry to monitor changes in muscle strength. Results:We included 37 persons (mean age 43 years, range 18-79 years) with HypoPP-causing variants in CACNA1S. Three participants were asymptomatic carriers, 22 had periodic paralysis, 3 had permanent weakness, and 9 had periodic paralysis in combination with permanent weakness. The median follow-up time was 20 months (range 12-25). We found that fat fraction increased in 10 of 21 examined muscles. An increase in the composite fat fraction of at least 1 muscle group was found in all symptomatic phenotypes. By contrast, we found no significant change in muscle strength. Discussion:The results from this follow-up study support the use of quantitative muscle MRI to monitor subclinical disease progression in HypoPP in patients with and without attacks of paralysis.

MADD is a treatable disorder of fatty acid oxidation.In the last eight years we have diagnosed 10 patients with adult-onset MADD in our part of Sweden, Sydöstra sjukvårdsregionen, with a population of just over one million people.This makes MADD the most common fatty oxidation diagnosis in adults in the area.The age of onset ranges from 22 to 74 years of age (mean 45) and 70% are female.Eight patients presented with proximal muscular weakness, often more pronounced in the legs than arms.Four patients also had weakness of the neck.Six patients had breathing problems, five had impaired sensory function whereas muscular fatigue or myalgia was experienced by four patients, respectively.Noted comorbidities were anxiety/depression (70%), chronic pain (40%), hypertension (30%) and hypothyroidism (20%).Seven patients were on medication with sertraline, four on cobalamin and folic acid and two on levothyroxine.All patients had slightly elevated creatine kinase (CK).Muscle biopsy showed increased amount of neutral lipids within muscle fibers in all patients.Acylcarnitine profiles in plasma showed a typical pattern for MADD in all patients.Neurophysiology showed myopathy in six patients and a sensory axonal neuropathy in three.A thorough genetic investigation was performed in 7 patients, but a genetic cause was only found in one of the patients, suggesting a non-genetic aetiology.All patients were treated with riboflavin, 150-400 mg/day (mean 255 mg/d).Two patients received carnitine 2g/day, and one patient Q10, in addition.Treatment resulted in full recovery of three and improvement in six patients.Sensory symptoms did not ameliorate.The CK was normalised in all patients and acylcarnitines were improved.Results from individual patients will be presented.

BACKGROUND:Genetic variants in titin (TTN) are associated with dilated cardiomyopathy (DCM) and skeletal myopathy. However, the skeletal muscle phenotype in individuals carrying heterozygous truncating TTN variants (TTNtv), the leading cause of DCM, is understudied. OBJECTIVES:This study aimed to assess the skeletal muscle phenotype associated with TTNtv. METHODS:Participants with TTNtv were included in a cross-sectional study. Skeletal muscle fat fraction was evaluated by magnetic resonance imaging (compared with healthy controls and controls with non-TTNtv DCM). Muscle strength was evaluated by dynamometry and muscle biopsy specimens were analyzed. RESULTS:Twenty-five TTNtv participants (11 women, mean age 51 ± 15 years, left ventricular ejection fraction 45% ± 10%) were included (19 had DCM). Compared to healthy controls (n = 25), fat fraction was higher in calf (12.5% vs 9.9%, P = 0.013), thigh (12.2% vs 9.3%, P = 0.004), and paraspinal muscles (18.8% vs 13.9%, P = 0.008) of TTNtv participants. Linear mixed effects modelling found higher fat fractions in TTNtv participants compared to healthy controls (2.5%; 95% CI: 1.4-3.7; P < 0.001) and controls with non-TTNtv genetic DCM (n = 7) (1.5%; 95% CI: 0.2-2.8; P = 0.025). Muscle strength was within 1 SD of normal values. Biopsy specimens from 21 participants found myopathic features in 13 (62%), including central nuclei. Electron microscopy showed well-ordered Z-lines and T-tubuli but uneven and discontinuous M-lines and excessive glycogen depositions flanked by autophagosomes, lysosomes, and abnormal mitochondria with mitophagy. CONCLUSIONS:Mild skeletal muscle involvement was prevalent in patients with TTNtv. The phenotype was characterized by an increased muscle fat fraction and excessive accumulation of glycogen, possibly due to reduced autophagic flux. These findings indicate an impact of TTNtv beyond the heart.

The three major collagen VI genes: COL6A1, COL6A2, and COL6A3 encode microfibrillar components of extracellular matrices in multiple tissues including muscles and tendons. Pathogenic variants in the collagen VI genes cause collagen VI-related dystrophies representing a continuum of conditions from Bethlem myopathy at the milder end to Ullrich congenital muscular dystrophy at the more severe end. Here we describe a pathogenic variant in the COL6A1 gene (NM_001848.3; c.1741-6G>A) found in homozygosity in three patients with Ullrich congenital muscular dystrophy. The patients suffered from severe muscle impairment characterised by proximal weakness, distal hyperlaxity, joint contractures, wheelchair-dependency, and use of nocturnal non-invasive ventilation. The pathogenicity was verified by RNA analyses showing that the variant induced aberrant splicing leading to a frameshift and loss of function. The analyses were in line with immunocytochemistry studies of patient-derived skin fibroblasts and muscle tissue demonstrating impaired secretion of collagen VI into the extracellular matrix. Thereby, we add the variant c.1741-6G>A to the list of pathogenic, recessive, splice variants in COL6A1 causing Ullrich congenital muscular dystrophy. The variant is listed in ClinVar as of "uncertain significance" and "likely benign" and may presumably have been overlooked in other patients.

Background and objectives Primary hypokalemic periodic paralysis (HypoPP) is an inherited channelopathy most commonly caused by mutations in CACNA1S . HypoPP can present with different phenotypes: periodic paralysis (PP), permanent muscle weakness (PW), and mixed weakness (MW) with both periodic and permanent weakness. Little is known about the natural history of HypoPP. Methods In this 3-year follow-up study, we used the MRC scale for manual muscle strength testing and whole-body muscle MRI (Mercuri score) to assess disease progression in individuals with HypoPP-causing mutations in CACNA1S. Results We included 25 men (mean age 43 years, range 18–76 years) and 12 women (mean age 42 years, range 18–76 years). Two participants were asymptomatic, 21 had PP, 12 MW, and two PW. The median number of months between baseline and follow-up was 42 (range 26–52). Muscle strength declined in 11 patients during follow-up. Four of the patients with a decline in muscle strength had no attacks of paralysis during follow-up, and two of these patients had never had attacks of paralysis. Fat replacement of muscles increased in 27 patients during follow-up. Eight of the patients with increased fat replacement had no attacks of paralysis during follow-up, and two of these patients had never had attacks of paralysis. Discussion The study demonstrates that HypoPP can be a progressive myopathy in both patients with and without attacks of paralysis.

We investigated the humoral response to the Pfizer-BioNTech COVID-19 (BNT162b2) vaccine in patients with myasthenia gravis on or off immunosuppressants and compared this to the response in healthy individuals. The SARS-CoV-2 IgG response and neutralizing capacity were measured in 83 patients (57 on immunosuppressants) and 332 healthy controls at baseline, three weeks, and two and six months after the vaccine. We found that the proportion of positive humoral response was lower in patients on immunosuppressants vs. controls at three weeks and two months (p ≤ 0.001), but not at six months post-vaccination (p = 0.379).